Search PubMed⌕ Search

Biomedical subjects

B O'Malley

Publications and source records attributed to B O'Malley.

At least 19 recordsLinked to original sources
PubMed2006

Topological characterization of crystallization of gold nanoclusters.

In this study we use a new topological structure measure to analyze the local environment of 923 atom gold clusters quenched from the melt, at various quench rates, by molecular dynamics. The crystallization and geometrical rearrangements of the core atoms upon freezing can be clearly observed using our structure measure which is based on planar graphs. Our results support the hypothesis that crystallization is initiated from the surface and proceeds into the cluster core.

Journal Article↗
PubMed2005

The microstructure of di-alkyl chain cationic/nonionic surfactant mixtures: observation of coexisting lamellar and micellar phases and depletion induced phase separation.

The evolution of the microstructure and composition occurring in the aqueous solutions of di-alkyl chain cationic/nonionic surfactant mixtures has been studied in detail using small angle neutron scattering, SANS. For all the systems studied we observe an evolution from a predominantly lamellar phase, for solutions rich in di-alkyl chain cationic surfactant, to mixed cationic/nonionic micelles, for solutions rich in the nonionic surfactant. At intermediate solution compositions there is a region of coexistence of lamellar and micellar phases, where the relative amounts change with solution composition. A number of different di-alkyl chain cationic surfactants, DHDAB, 2HT, DHTAC, DHTA methyl sulfate, and DISDA methyl sulfate, and nonionic surfactants, C12E12 and C12E23, are investigated. For these systems the differences in phase behavior is discussed, and for the mixture DHDAB/C12E12 a direct comparison with theoretical predictions of phase behavior is made. It is shown that the phase separation that can occur in these mixed systems is induced by a depletion force arising from the micellar component, and that the size and volume fraction of the micelles are critical factors.

Journal Article↗
PubMed2003

How much of a priority is treating erectile dysfunction? A study of patients' perceptions.

BACKGROUND: Erectile dysfunction (ED) is one complication of diabetes for which the treatment is rationed. Despite considerable public debate there has been no formal assessment of the views of patients and sufferers of the priority of treating ED. AIMS: To determine the perceptions of diabetic patients of the relative priority of treating ED in comparison with treatments for other diabetic complications and common medical conditions. METHODS: Psychological measures were used to assess subjects' perceptions of the relative importance of ED in comparison with eight other common problems (blindness, foot ulcers, high blood pressure, impotence, kidney disease, high cholesterol, migraine, mild indigestion and sleeping difficulties). The concept of willingness to pay was used to assess the amount per month participants would be prepared to pay for treatment for ED and other conditions. Four groups (controls, healthy diabetic men, impotent diabetic men and impotent diabetic men not in a sexual relationship) were studied. RESULTS: Significant differences were found between the four groups with regard to the ranking of the importance of ED compared with other health problems. Impotent diabetic male patients were prepared to pay more for treatment for their condition than all other conditions except blindness and renal failure. CONCLUSIONS: Men with diabetes, in particular ED sufferers, believe ED has a major impact on quality of life and is as important to treat as many other conditions associated with diabetes.

Adaptation, Psychological↗
PubMed2001

Differential gene expression in a murine model of cancer cachexia.

Murine adenocarcinoma 16 (MAC16) tumors and cell lines induce cachexia in NMRI nude mice, whereas histologically similar MAC13 tumors do not. After confirming these findings in BALB/c nude mice, we demonstrated that this tissue wasting was not related to decreased food intake or increased total body oxidative metabolism. Previous studies have suggested that MAC16's cachexigenic properties may involve the production of tumor-specific factors. We therefore screened for genes having increased expression in the MAC16 compared with the MAC13 cell line by performing hybridization to a murine cDNA expression array, by generation and comparison of cDNA libraries from each cell line, and by PCR-based subtractive hybridization. Northern blot hybridization was performed to confirm differences in transcript expression. Transcripts encoding insulin-like growth factor binding protein-4, cathepsin B, ferritin light and heavy chain, endogenous long-terminal repeat sequences, and a viral envelope glycoprotein demonstrated increased expression in the MAC16 cell line. The roles of a number of these genes in known metabolic pathways identify them as potential participants in the induction of cachexia.

Adenocarcinoma↗
PubMed1999

Activation of PPARgamma coactivator-1 through transcription factor docking.

Transcriptional coactivators have been viewed as constitutively active components, using transcription factors mainly to localize their functions. Here, it is shown that PPARgamma coactivator-1 (PGC-1) promotes transcription through the assembly of a complex that includes the histone acetyltransferases steroid receptor coactivator-1 (SRC-1) and CREB binding protein (CBP)/p300. PGC-1 has a low inherent transcriptional activity when it is not bound to a transcription factor. The docking of PGC-1 to peroxisome proliferator-activated receptor gamma (PPARgamma) stimulates an apparent conformational change in PGC-1 that permits binding of SRC-1 and CBP/p300, resulting in a large increase in transcriptional activity. Thus, transcription factor docking switches on the activity of a coactivator protein.

Animals↗
PubMed1999

Resistance to several steroids in two sisters.

A 14-yr-old native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of apparent mineralocorticoid excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens, but no resistance to vitamin D or thyroid hormones. She lacked Cushingoid features despite significantly high cortisol levels. Menstruation was regular, and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly due to a coactivator defect.

Adolescent↗
PubMed1998

Giant cell tumour of the retropharynx.

AIMS: Giant cell tumours of soft tissues are usually of tenosynovial origin and are benign, slow growing neoplasms that have the capacity for local recurrence. They occur most frequently in the fingers and only rarely in the head and neck region. Their occurrence in the retropharynx has not been reported. The differential diagnoses of head and neck lesions containing giant cells are discussed. METHODS AND RESULTS: We describe a case of a retropharyngeal giant cell tumour of tenosynovial type in a 48-year-old man. The clinical, radiological and histological features are reviewed. Immunohistochemical studies point to a possible histiocytic origin based on reactivity for CD68. CONCLUSIONS: Tenosynovial giant cell tumour should be considered in the differential diagnosis of tumours arising in the retropharyngeal soft tissues.

Antigens, CD↗
PubMed1998

Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Myeloperoxidase mRNA analysis in acute lymphoblastic leukemia.

Expression of the myeloperoxidase (MPO) gene at the mRNA level is a better lineage marker than enzymatic activity in early myeloid precursors and their leukemic counterparts. Its diagnostic use depends on the specificity of expression for myeloblasts and its absence in blasts of lymphoid lineage. The present study investigates MPO mRNA expression in adult acute lymphoblastic leukemia (ALL), using reverse transcription-polymerase chain reaction. Of a total of 13 cases, six were found to have blasts positive for MPO mRNA; in all of these cases, the blasts were cytochemically negative for MPO. This unexpected finding of MPO mRNA positivity in six of 13 cases was further investigated at the molecular level. Bcr gene rearrangement analysis was positive in all six cases for the bcr breakpoint diagnostic of chronic myelogenous leukemia (CML). Only three of these six cases were cytogenetically positive for a Philadelphia (Ph) chromosome. Based on molecular analysis, these cases are considered as CML presenting in blast crisis of lymphoid lineage, as opposed to de novo ALL. The remaining seven cases were Ph negative at the cytogenetic and molecular levels; the leukemic blasts were MPO mRNA negative, confirming the lack of MPO gene expression in de novo ALL.

Adult↗
PubMed1996

Is there a role for high-dose chemotherapy with stem cell rescue for brain stem tumors of childhood?

Diffuse pontine tumors are highly lethal and conventional therapy with irradiation provides long-term survival to a very small proportion of the patients. We have reported promising results using high-dose chemotherapy with autologous stem cell rescue in patients with recurrent high-grade astrocytomas in other anatomic locations, but our results and those of others have been very discouraging in children with brain stem tumors. Alternative strategies need to be developed for this highly lethal disease.

Adult↗
PubMed1995

Recombinant antibodies in bioactive peptide design.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is important in many immune and inflammatory processes. GM-CSF binds to specific cellular receptors which belong to a recently described supergene family. These receptors are potential targets for pharmacologic design, and such design depends on a molecular understanding of ligand-receptor interactions. One approach to dissecting out critical intermolecular interactions is to develop analogs of specific interaction sites of potential importance. Monoclonal antibodies have been employed for these purposes in prior studies. Here we present application of recombinant antibody technology to the development of analogs of a site on GM-CSF bound by a neutralizing anti-GM-CSF monoclonal antibody. Polyclonal antisera with high titer neutralizing activity against human GM-CSF were developed in BALB/c mice. Purified immunoglobulins were prepared and used to immunize syngeneic mice. Anti-anti-GM-CSF was developed which demonstrated biological antagonist activity against GM-CSF-dependent cellular proliferation. RNA was extracted from spleen cells of mice with biologically active anti-anti-GM-CSF, cDNA synthesized, and polymerase chain reaction performed with primers specific for murine kappa light chain V regions. Polymerase chain reaction products were cloned into the pDABL vector and an expression library developed. This was screened with anti-GM-CSF neutralizing mAb 126.213, and several binding clones isolated. One clone (23.2) which inhibited 126.213 binding to GM-CSF was sequenced revealing a murine kappa light chain of subgroup III. Comparison of the 23.2 sequence with the human GM-CSF sequence revealed only weak sequence similarity of specific complementarity determining regions (CDRs) with human GM-CSF. Structural analysis revealed potential mimicry of specific amino acids in the CDR I, CDR II and FR3 regions of 23.2 with residues on the B and C helices of GM-CSF. A synthetic peptide analog of the CDR I was bound by 126.213, specifically antagonized GM-CSF binding to cells and blocked GM-CSF bioactivity. These studies indicate the feasibility of using recombinant antibody libraries as sources of interaction site analogs.

Amino Acid Sequence↗
PubMed1995

Gene transfer to synovial cells by intra-articular administration of plasmid DNA.

We studied reporter gene expression in synovial tissue after intra-articular administration of an expression plasmid into the knees of rabbits and rats. In both species, administration of a plasmid encoding beta-galactosidase led to gene expression in the synovial cells lining the joint. Expression correlated with the presence of plasmid DNA in synovial tissue extracts. Studies with a plasmid encoding chloramphenicol acetyltransferase demonstrated that gene expression persists for 2-5 days after administration. Southern blotting demonstrated that the administered plasmid was taken up rapidly by synovial tissue and degraded. By 24 hr after administration, no intact plasmid could be detected by Southern blotting, although small amounts of plasmid could be amplified by PCR up to 7 days. Administration of a plasmid encoding human growth hormone demonstrated that this product could be expressed from synovial cells and secreted into the synovial fluid. The histological distribution of gene expression in synovium resembles the known distribution of particulate materials injected into the joint and suggests that plasmid DNA is taken up by nonspecific endocytosis like other particulate materials during the remodeling of synovial fluid.

Animals↗
PubMed1991

Production of transgenic mice from cryopreserved fertilized ova.

Cryopreserved fertilized mouse ova were used to generate transgenic mice via micromanipulation. Five-DNA constructions were injected into a total of 1,052 cryopreserved ova, of which 683 (65%) survived the injection and were transferred into recipients. Of 35 recipients, 66% became pregnant and littered a total of 88 pups. As controls, these DNA constructions were also injected into 1,123 fresh ova, of which 744 (66%) survived and were transferred. Of 42 recipients, 79% became pregnant and littered a total of 167 pups. That is, 22% of fresh ova that were transferred developed into live pups, whereas only 13% of cryopreserved ova did so. Of the pups born, 42 of the 167 (25%) produced from fresh ova were transgenic, and 28 of the 88 (32%) produced from cryopreserved ova were transgenic. In terms of the injected ova that had been transferred, 5.6% of the 744 fresh and 4.1% of the 683 frozen ova developed into transgenic mice. These data indicate that the efficiency of production of transgenic mice from cryopreserved ova is close to that from fresh ova. That observation and the fact that cryopreserved ova allow more efficient utilization of animals suggest that cryopreserved ova can be used instead of fresh ova to produce transgenic mice.

Animals↗
PubMed1991

Infant feeding practices of migrant farm laborers in northern Colorado.

The purpose of this study was to provide descriptive information on migrant farm laborers' infant feeding practices in northern Colorado. We used a survey questionnaire to interview 49 families with a 6- to 23-month-old child who was enrolled in the Migrant Head Start Center. Sixteen (33%) of the mothers breast-fed their infants, but only five (14%) of the 35 Mexican Americans breast-fed. Thirty-four (69%) of the mothers used formula and seven (14%) gave their child cow's milk at birth. Introduction of solids occurred at a mean of 6.6 months. Of the respondents, 13 (27%) introduced solids before 4 months of age, whereas 29 (59%) introduced solids before the age of 6 months. Thirty-six (73%) of the migrants put their child to bed with a sweetened beverage, milk, or formula in a bottle. Diarrhea in the children was reported by 39 (80%) of the migrants, with 15 (31%) stating that it occurred at least once per month. One third (n = 16) of the respondents reported that their children had constipation lasting 1 to 14 days, but for most (n = 10) it occurred less than once per month. Results suggest that migrant families need more dietary recommendations about breast-feeding, introduction of liquids/solid foods, proper formula preparation, avoidance of baby bottle tooth decay, and treatment of diarrhea and constipation.

Breast Feeding↗