Search PubMed⌕ Search

Biomedical subjects

K Brady

Publications and source records attributed to K Brady.

At least 37 records · Page 2Linked to original sources

Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996.

Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRAPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies, highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.

Amino Acid Sequence↗

Pharmacologic hemoglobin reversal: the importance of lipid intermediaries and the proposed involvement of the cAMP and phosphatidylinositol second messenger systems.

Humoral and microenvironmental influences have played a major role in recent research into reversing the Hb F to Hb A switch. Early research in this area focused on hormonal influences and showed both thyroid hormone and prolactin could induce small but statistically significant reversals in hemoglobin phenotype. Recent research has focused on the effect of certain lipids in this process. The current study shows a synergy between thyroid hormone and prolactin in inducing a significant switch in adult rat hemoglobin patterns toward the neonatal pattern. Further, it is hypothesized that this synergy is due to the hormones' effect on lipid intermediaries whose effect in turn are proposed to be mediated by the cAMP and phosphatidylinositol second messenger systems.

Animals↗

Mineral trioxide aggregate stimulates a biological response in human osteoblasts.

We report a novel material that appears to stimulate cytokine production in human osteoblasts and allow good adherence of the cells to the material. We have examined cultured osteoblasts (MG-63) in the presence of mineral trioxide aggregate (MTA) as set in moist conditions; secondly, we examined the behavior of these MG-63 cells with respect to cytokine and osteocalcin production and alkaline phosphatase activity. Standard ELISA assays were used for assessment of interleukin (IL)-1 alpha, IL-1 beta, IL-6, macrophage colony stimulating factor (M-CSF), and osteocalcin. Furthermore the levels of alkaline phosphatase were measured to establish the level of differentiation of the cells. Cells without MTA served as controls. Cells also were grown in the presence of polymethylmethacrylate (PMA), the commonly used orthopedic cement. In all dishes cells were seen adhering to the base and MTA at 6 h and had increased to confluence at 144 h. IL-1 alpha (175.1 +/- 32.6 pg/mL), IL-1 beta (154.0 +/- 26.7 pg/mL), and IL-6 (214.7 +/- 21.8 pg/mL) were raised when the cells were grown in the presence of MTA at 144 h, with raised values at all time intervals. M-CSF appeared to be unaffected although the overall value was high (7,045.0 +/- 89.5 pg/mL). In contrast, cells grown in the absence of MTA produced negligible amounts of these cytokines (< pg/mL) as did those cells grown in the presence of PMA. Osteocalcin production increased when cells were grown on MTA from 3.8 +/- 0.87 ng/mL to 19.7 +/- 2.8 ng/mL. No osteocalcin could be detected with PMA. Cells in contact with MTA also appeared to have levels of alkaline phosphatase similar to those reported elsewhere (4.3 +/- 0.21 mumol/mg protein/min). No cells could be found attached to PMA and so no alkaline phosphatase activity could be measured.

Alkaline Phosphatase↗

Dual diagnosis in primary care. Detecting and treating both the addiction and mental illness.

The initial phase of treatment includes engaging the patient in a discussion about the doctor's concerns and providing patients with information about the problems as well as the possibility of change. Treatment of dual disorders often requires a heightened awareness of the consequences of the problem and the development of a realistic plan for change. The treatment plan must attempt to evaluate and treat the addiction and the psychiatric and medical illnesses.

Anxiety Disorders↗

Myelodysplastic syndrome presenting with clonal rearrangement isolated to chromosomal region 1q.

Myelodysplastic syndrome (MDS) is a malignant hematologic disorder that may present with clinical features consistent with the diagnosis of severe aplastic anemia (SAA). Distinguishing the two disorders may depend on the presence of a clonal chromosomal abnormality. In the following, we report a case of MDS associated with what we believe to be a previously unreported clonal abnormality of chromosome 1q, a finding that enabled us to distinguish between MDS and SAA.

Adult↗

Multiple myeloma arising from monoclonal gammopathy of undetermined significance in a patient with Gaucher's disease.

We report the case of a 64-year-old woman who, 12 years after receiving a diagnosis of Gaucher's disease with concurrent monoclonal gammopathy of undetermined significance, developed worsening thrombocytopenia and bone pain. Bone marrow biopsy at this time revealed 50% plasma cells with a serum monoclonal immunoglobulin A-lambda level of 3.2 g/L. Roentgenography revealed a lytic clavicular lesion, and a diagnosis of multiple myeloma was made. To our knowledge, this case is the first to document the evolution of a monoclonal gammopathy of undetermined significance to multiple myeloma in a patient with Gaucher's disease. The importance of investigating cytopenias and increased bone pain in such patients, perhaps by bone marrow biopsy, to rule out potentially malignant plasma cell dyscrasias is stressed.

Bone Marrow↗

The Children's Affective Lability Scale: a psychometric evaluation of reliability.

The Children's Affective Lability Scale (CALS) is a 20-item parent report measure developed to assess affect regulation in children aged 6-16. It was normed with school children in regular education classrooms and with children hospitalized in a psychiatric facility. Internal-consistency reliability, split-half reliability, and two-week test-retest reliability were excellent. Staff interrater reliability in the psychiatric sample was acceptable. Higher CALS scores were observed in an in-patient psychiatric sample than in either an out-patient or a normative sample. A principal components factor analysis yielded two components for the normative sample.

Adolescent↗

Psychometric characteristics of the Children's Motivation Scale.

A 16-item Children's Motivation Scale (CMS) was developed to evaluate level of motivation in children and adolescents. The study population consisted of a normative sample of 290 school children and a clinical sample of 165 child and adolescent psychiatric patients. Test-retest, internal consistency, and interrater reliability were fair to good for both samples. Validity of the CMS was demonstrated by its ability to differentiate clinical from normative samples according to the level of motivation, by a significant correlation of the CMS with an independent measure of withdrawal, and by its lack of correlation with an independent measure of depression. Principal components analysis identified a three-component structure. These findings support the conclusion that the CMS accesses a clinically important but often overlooked psychiatric construct.

Adolescent↗

Thoracoscopic pleurodesis with minocycline vs talc in the porcine model.

BACKGROUND: Eighteen adult pigs (Sus scrofa) underwent thoracoscopy and were placed into one of three groups: no sclerosant, talc pleurodesis, or minocycline pleurodesis. METHODS: Animals were then sacrificed at matched time intervals. Gross inspection of the pleural cavity estimated percentage of pleural symphysis (>25% was considered substantial) and allowed assignment of a pleurodesis score based on a scale described by Bresticker. Microscopic examination evaluated degree of fibrosis as mild, moderate, or severe. RESULTS: The talc group had significantly better pleurodesis than the minocycline group as determined by (1) the proportion of animals with substantial surface pleural symphysis (5/6 vs 1/6, p < 0.01), (2) a higher pleurodesis score (3 vs 1.3, p < 0.05), and (3) the proportion of animals with moderate fibrosis (5/6 vs 0/6, p < 0. 01). CONCLUSIONS: The authors conclude that instillation of aerosolized talc produces significantly better fibrosis and pleural symphysis than atomized minocycline in this animal model.

Animals↗

Acquired immunodeficiency syndrome and ocular calcification.

We report the presence of peculiar nonbanded calcification of the cornea in three patients with acquired immunodeficiency syndrome, discovered on postmortem histological examination of the globes. In one patient, multiple calcium salt precipitates also affected other ocular and orbital structures. Calcium deposits were present in the corneal stroma but spared Bowman's layer, as is usually seen in primary and secondary corneal calcification. The calcified areas were positive to von Kossa, alizarin red, alcian blue, and colloidal iron stains. Electron probe analysis of the three cases showed the presence of calcium and phosphorus in a ratio characteristic for hydroxyapatite. No predisposing factors could be found. The possible role of associated alterations in the mucopolysaccharide content or composition in the calcified areas is unclear.

Acquired Immunodeficiency Syndrome↗

Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35.

The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1 beta converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.

Amino Acid Sequence↗

Ability of normal vaginal flora to produce detectable phosphatidylglycerol in amniotic fluid in vitro.

OBJECTIVE: To determine if bacteria are capable of producing phosphatidylglycerol in amniotic fluid (AF) and the number of colony forming units (CFU) of bacteria necessary to produce this result. METHODS: Eleven species of bacteria and one species of yeast, common to the female genital tract and implicated in chorioamnionitis, were selected. Amniotic fluid was collected from 21 women and inoculated with 10(8) CFU/mL of each isolate. Aliquots of AF were tested at 0, 4, 12, and 24 hours for colony counts and the presence of phosphatidylglycerol by thin-layer chromatography. RESULTS: The mean gestational age (+/- standard deviation) of the 21 study patients was 33 weeks and 1 day (+/- 4 weeks). Among the 12 species studied, Escherichia coli produced phosphatidylglycerol, at a concentration of 1.75 x 10(8) CFU/mL, beginning 12 hours after incubation. CONCLUSION: Escherichia coli is capable of producing phosphatidylglycerol in AF in vitro and is present in the vagina in 24% of normal pregnant patients. Our findings question the validity of using vaginal pool AF specimens for phosphatidylglycerol determination. Therefore, we recommend that patients presenting with preterm premature rupture of membranes be evaluated by amniocentesis to determine fetal lung maturity with phosphatidylglycerol and the lecithin-sphingomyelin ratio.

Amniotic Fluid↗

Sonographic assessment of amniotic fluid in normal twin pregnancy.

A sonographic standard for assessment of amniotic fluid volume in normal twin pregnancy is provided. In 210 uncomplicated twin pregnancies, amniotic fluid volume was assessed sonographically, by measuring the total amniotic fluid index (AFI), as well as the deepest single vertical pocket in each sac. The mean AFI was greater than values found in singleton gestations; the AFI increased up to 27 weeks' gestation, and decreased thereafter. It correlated well with measurement of the deepest vertical pocket in each sac (r = 0.71; p < 0.0001). In twin pregnancy at 26 to 32 weeks' gestation a fluid pocket of at least 8 cm was found in 9.8% of cases and did not indicate pathologic states. Either AFI or measurement of the deepest fluid pocket in each sac can be used to assess fluid volume in twin pregnancy. A table specific to twin pregnancy should be used when evaluating twin gestations sonographically.

Amniotic Fluid↗

Fortuitous imaging of a primary adrenocortical carcinoma with Tc-99m HDP.

The importance of evaluating nonfunctional adrenal masses in the right clinical setting is discussed. A 60-year-old man was initially diagnosed of having a localized lung carcinoma. Metastatic work-up showed an adrenal mass that was not deemed to be related to the lung primary. Although biochemical testing revealed that the adrenal mass was nonfunctional, adrenal scintigraphy was not performed. On resection, the lung neoplasm was shown to be a poorly differentiated adenocarcinoma. Radiologic follow-up of the adrenal finding was recommended. A year later, the patient presented with an abdominal mass that was visualized by bone scintigraphy and, on resection, proved to be adrenocortical carcinoma. In retrospect, the lung mass was a metastasis of an adrenocortical carcinoma.

Adenocarcinoma↗

Intraosseous secondary calcium salt crystal deposition: an artefact of acid decalcification.

We previously observed, in decalcificated bone specimens, intraosseous crystal deposits with morphological and analytical similarity to calcium pyrophosphate dihydrate. We have now been able, by a combination of more detailed morphological studies of these and similar cases, and by infrared spectroscopy in three cases, to show that this is, in fact deposition of the secondary calcium salts brushite and monetite, occurring as an artefact during formic acid decalcification. Our earlier postulate of bone as an additional primary crystallization site for calcium pyrophosphate dihydrate is effectively disproved. This artefact deserves wider recognition.

Artifacts↗

Calcium oxalate crystal deposition in epithelioid histiocytes of granulomatous lymphadenitis: analysis by light and electronmicroscopy.

In this study of 55 cases of granulomatous lymphadenitis of various aetiologies, both haematoxylin and eosin stained and unstained sections were examined by light and polarizing light microscopy for crystals within epithelioid histiocytes. This investigation was prompted by a case of granulomatous lymphadenitis in which the identification of ovoid birefringent structures within epithelioid histiocytes led to an initial false suggestion of foreign body reaction. Identical single, small, ovoid or biconvex, intensely birefringent crystals, invisible by ordinary light microscopy, were found within the cytoplasm of mononuclear epithelioid histiocytes in 37 cases. There was only minor crystal loss with routine H & E staining. The sections were also examined by scanning electronmicroscopy in secondary and backscattered electron imaging modes and 27 cases were found to contain biconvex crystals which were shown on X-ray energy dispersive spectroscopic microanalysis to be consistent with calcium oxalate. There was a good quantitative correlation between light and scanning electron microscopy. Tissue from the index case was also examined by transmission electronmicroscopy, and electron dense crystals were identified. We confirm the previous findings of ovoid oxalate crystals in a variety of granulomatous conditions including Mycobacterial infection, sarcoidosis and Crohn's disease. Ovoid crystals of calcium oxalate, a common finding in granulomatous lymphadenitis, appear to be endogenously derived, and should be more widely recognized in order to avoid misdiagnosis of foreign body reaction.

Calcium Oxalate↗