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Biomedical subjects

M Roberts

Publications and source records attributed to M Roberts.

At least 253 records · Page 14Linked to original sources
PubMed1988

Structure and function of the pS2 gene and estrogen receptor in human breast cancer cells.

The role of estrogen in the growth of human breast cancers has been investigated at two levels. First, we have studied the pS2 gene, whose transcription is stimulated by estrogen in the human breast cancer cell line, MCF-7. The pS2 gene product is a small, secreted polypeptide currently of unknown function, but with structural features similar to some growth factors. The expression of the pS2 gene has so far been detected only in MCF-7 cells and some breast cancer biopsies. Preliminary studies indicate that pS2 is a potential marker for hormone-dependent breast cancer. Ongoing studies will continue to focus on the implicated role of pS2 in the estrogen-mediated growth of breast cancers and its possible use as a marker for estrogen-dependent tumors. Second, we have analyzed the structure and function of the human ER. The receptor stimulates pS2 gene transcription by interacting with an ERE in the 5'-flanking region of that gene. A mutational analysis of the receptor protein has localized a DNA-binding domain, which determines target gene specificity, and a hormone-binding domain. These domains appear to be the only two regions of the receptor which are absolutely required for the transcription-activating function of the ER in transfection assays with reporter plasmids. The N-terminal region of the protein (regions A and B), which is necessary for increasing the efficiency of gene expression using the pS2 ERE, but not a vitellogenin ERE, may also play a role in transcription activation. Further progress in the characterization of the ER functional domains will require studies on target genes in a more physiological chromatin environment, as well as detailed physical analyses of receptor structure.

Amino Acid Sequence↗
PubMed1988

Immune responses to Aspergillus in cystic fibrosis.

Aspergillus fumigatus (Af) is well recognized in its ability to colonize the respiratory tract in cystic fibrosis (CF). Furthermore, a number of the immune responses of the patient with CF to this organism have been characterized, and the immune inflammatory response to Af may result in allergic bronchopulmonary aspergillosis (ABPA). This study evaluated a series of immunologic parameters in 75 patients with CF in order to characterize more fully the spectrum of immune responses of those patients to Af and to clarify the relationship of those responses to the clinical features of ABPA. The patients could be classified into four groups, depending on the clinical and immunologic findings. Eight (10.7%) of the 75 patients had clinical and laboratory evidence of ABPA, including immediate cutaneous reactivity to Af, eosinophilia, elevated total serum IgE, elevated serum IgE-Af or IgG-Af, and precipitating antibody to Af. Ten (13.3%) patients had these features, except that the total serum IgE level was within the normal range. Forty (53.5%) of the patients had no significant criteria for ABPA but had varying immunologic responses to Af, such as immediate cutaneous reactivity to Af in 25 patients and elevated serum IgE-Af and/or IgG-Af in 19 patients. Seventeen (22.7%) patients had no evidence of an immunologic response, as determined by skin testing and serologic assays. The study demonstrated that the response of patients with CF to Af ranges from clinically apparent ABPA to a possible variant of ABPA, to a nondiagnostic group of features consistent with sensitization to Af or to no characteristic immune response.

Adolescent↗
PubMed1988

Woodman's disease: hypersensitivity pneumonitis from cutting live trees.

A 28-year-old man developed multiple episodes of fever, cough, shortness of breath, and leukocytosis several hours after cutting live oak and maple trees. Fungal cultures of wood chips from oak and maple trees were positive for Penicillium (three species), Paecilomyces sp., Aspergillus niger, Aspergillus sp., and Rhizopus sp. Gel-immunodiffusion studies demonstrated serum precipitins to extracts of oak chips, Penicillium sp., and Paecilomyces sp., and suggested that Penicillium sp. and Paecilomyces sp. shared cross-reactive antigens that were the significant antigens in the oak chips. ELISA studies demonstrated elevated serum levels of IgG to an oak chip extract, inhibition of that ELISA by preincubation of serum with Penicillium sp., and absence of elevated IgG levels to an extract of freshly cut oak wood that had been stripped of bark to minimize mold contamination. The case analysis indicates that the patient likely had hypersensitivity pneumonitis on exposure to Penicillium sp., when he was cutting trees, and identifies cutting live trees as another occupational exposure that may cause hypersensitivity pneumonitis.

Adult↗
PubMed1988

Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen-specific antibodies and total IgE.

Bronchoalveolar lavage (BAL) was performed in eight patients with allergic bronchopulmonary aspergillosis (ABPA) at a time when chest roentgeongraphy did not reveal an infiltrate, and respiratory status was stable. BAL was tolerated well by all patients with only one patient experiencing mild wheezing. BAL fluid recovery averaged 40%, and total cells/lavage were 22.3 x 10(6) (range 3.5 to 49.5 x 10(6)). Cell viability, as determined by trypan blue exclusion, averaged 48% (range 34% to 60%). Mean values for cellular elements were macrophages, 62%; epithelial cells, 12%; lymphocytes, 16%; neutrophils (PMN), 4%; and eosinophils, 6%. Isotypic antibodies to Aspergillus fumigatus (Af) in BAL and serum were detected by an amplified indirect ELISA. Antibodies to Af in BAL expressed as optical density/albumin (milligrams per milliliter) were compared to BAL from six nonatopic patients. IgE-Af and IgA-Af in BAL were elevated in patients with ABPA compared with six nonatopic patients. The ratios of Ig-Af in BAL to peripheral blood in patients with ABPA were 48 (range 18 to 75) for IgE-Af, 96 (range 37 to 159) for IgA-Af, and 0.94 (range 0.24 to 1.40) for IgG-Af, suggesting local production of IgE-Af and IgA-Af in the bronchoalveolar compartment. Total serum IgE correlated directly with IgE-Af in BAL (rs = 0.67; p less than 0.02). However, the ratio of total BAL IgE/albumin divided by total serum IgE/albumin was 0.93 +/- 0.94, suggesting that the bronchoalveolar compartment is not the source of the significant elevations in total serum IgE in ABPA.

Antibodies, Fungal↗
PubMed1988

Diastolic abnormalities in young asymptomatic diabetic patients assessed by pulsed Doppler echocardiography.

Indexes of left ventricular diastolic filling were measured by pulsed Doppler echocardiography in 21 insulin-dependent diabetic patients and 21 control subjects without clinical evidence of heart disease. No patient had chest pain or electrocardiographic changes during exercise testing. The mean age of patients was 32 years. All patients had a normal ejection fraction. Six (29%) of the 21 diabetic patients had evidence of diastolic dysfunction as assessed by the presence of at least two abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in diabetic compared with control subjects (1.24 +/- 0.21 versus 1.66 +/- 0.30, p. less than 0.001). Atrial filling velocity was significantly increased in diabetic patients (74.3 +/- 16.7 versus 60.3 +/- 12.2 cm/s, p less than 0.004), whereas early filling velocity was reduced by a nearly significant degree (88.8 +/- 12.6 versus 98.5 +/- 18.8 cm/s, p less than 0.057). The atrial contribution to stroke volume as assessed by area under the late diastolic filling envelope compared to total diastolic area was also significantly increased in diabetic compared with control subjects (35 versus 27%, p less than 0.001). Left ventricular diastolic filling abnormalities in diabetic patients did not correlate with duration of diabetes, retinopathy, nephropathy or peripheral neuropathy. These data suggest that approximately one-third of such patients have subclinical myocardial dysfunction unrelated to accelerated atherosclerosis. Doppler echocardiography may offer a reliable noninvasive means to assess diastolic function and to follow up diabetic patients serially for any deterioration in cardiac status before the appearance of clinical symptoms.

Adult↗
PubMed1988

Blocking of acquisition and presentation of antigen by dendritic cells with cyclosporine. Studies with fluorescein isothiocyanate.

The effect of cyclosporine on the acquisition and presentation of antigen by dendritic cells (DC) was examined. Mice skin-painted with the contact sensitizer FITC received 100 mg/kg of CsA orally on the day before and the day of sensitization. This blocked the development of delayed hypersensitivity as measured by ear-swelling on challenge with antigen on day 6. The antigen-presenting DC in the draining lymph nodes 24 hr after skin painting were studied. The numbers of DC within the lymph node more than doubled after skin painting and this was not altered by the treatment with CsA. The DC from normal skin-painted animals showed a biphasic distribution of antigen, with more than half the cells acquiring high levels of antigen and the remainder having low amounts. In the animals treated with CsA most cells had low levels of antigen. The DC from untreated animals stimulated primary proliferative responses of syngeneic lymphocytes in vitro and initiated delayed hypersensitivity in recipient animals, but the DC from CsA-treated animals did not stimulate immune responses. Cyclosporine may, therefore, prevent acquisition and presentation of antigen by DC in addition to any direct effects on T and B cells.

Animals↗
PubMed1988

DNA probes for K-antigen (capsule) typing of Escherichia coli.

DNA restriction fragments derived from the polysaccharide biosynthesis regions of cloned Escherichia coli K1, K5, and K12 capsular antigen genes hybridized only with DNA of strains determined by conventional methods to be of the same K serotype. A probe derived from the common transport region hybridized to all encapsulated E. coli strains.

Antigens, Bacterial↗
PubMed1988

Clinical and biological features predict relapse hazard in childhood acute lymphoid leukemia.

Remarkable progress has been made in understanding the immunobiology, cytogenetic features and potential molecular pathogenetic mechanisms of childhood acute lymphoid leukemias (ALL). Studies of the expression of certain lineage restricted molecules on the surface of or within normal lymphoid cells and their malignant counterparts have been largely responsible for this advance, which has markedly improved the classification of ALL. These studies have disclosed previously unrecognized biologic heterogeneity and have shown that there are several different immunophenotypic subsets of ALL. Some of these subsets differ in their clinical and cytogenetic features, as well as in their responsiveness to modern therapy, underscoring the clinical relevance of such studies. A consideration of all of these features of ALL permits a more accurate assessment of prognosis for children with newly diagnosed disease and has permitted tailoring therapy based on expected relapse hazard. Recent cytogenetic studies have disclosed that clonal abnormalities are present in the blast cells of most children with ALL. Furthermore, such studies have demonstrated increasing numbers of non-random structural anomalies of chromosomes, some of which are specific for certain immunophenotypic species of ALL. Finally, molecular studies of some of these particularly informative cytogenetic anomalies in leukemic cells have suggested that proto-oncogenes are altered and/or activated as a consequence of chromosomal rearrangements.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1988

Symptom rating scale for assessing hyperthyroidism.

A hyperthyroid symptom scale (HSS) was designed and administered to ten subjects with untreated Graves' disease. All subjects had clinical and chemical evidence of hyperthyroidism and reproducible HSS scores of 20 or more points. During sequential treatments with propranolol hydrochloride (phase 2) followed by propylthiouracil (phase 3) there was a significant decline in the HSS scores at each phase. Accompanying the decrease in HSS scores was a decrease in heart rate, but there was no change in thyroid function test results at phase 2 and a decrease in heart rate, thyroid function test results, and goiter size at phase 3. This new scale includes ten categories of symptoms, it is sensitive to changes in both the adrenergic and metabolic components of hyperthyroidism, and it is useful in the clinical assessment and management of patients with thyrotoxicosis.

Adult↗
PubMed1987

Structure of the human oestrogen-responsive gene pS2.

The human pS2 gene, whose expression is restricted to breast cancer cells, and whose transcription is induced by oestrogen in the human breast cancer cell line MCF-7, has been cloned from both placental and MCF-7 cell DNA. The exon-intron organization has been established by electron microscopy using genomic DNA-cDNA or -mRNA hybrid duplexes and by sequencing the exons and exon-intron junctions. The overall organization within and around the pS2 gene is the same in placental and MCF-7 cell DNA and the exonic sequences are identical to those previously determined from the cDNA. The 5'-flanking region of the pS2 gene is also identical (with the exception of two base transitions) in the two tissues. Thus no gene rearrangement nor sequence modification has occurred in the pS2 gene of the malignant and polyploid MCF-7 cells. A TATA-box, a CAAT-box and a GC-rich motif are present in the 5'-flanking region of the pS2 gene, but the latter motif is unusually located between the TATA-box and the capsite. No significant homology could be detected between the 5' flanking sequences of the pS2 gene and those of other oestrogen-responsive genes from different species.

Amino Acid Sequence↗
PubMed1987

Plasma cell leukemia with an unusual karyotype and prolonged survival following oral alkylating agent therapy.

A patient with primary plasma cell leukemia (PCL) is presented who had an excellent response to high-dose cyclophosphamide and prolonged survival. The sole cytogenetic abnormality detected in the bone marrow was monosomy 18. Although this karyotypic aberration has been previously described in PCL, it generally occurs associated with additional abnormalities. The peripheral blood plasma cells from this patient reacted intracellularly with the monoclonal antibody OKM-1, which binds to myeloid cells at and above the level of myelocytes and to monocytes. This finding supports a common precursor cell for plasma cells and cells of the myelomonocytic lineage.

Chromosome Deletion↗
PubMed1987

Plasma cell leukemia with an unusual karyotype and prolonged survival with oral alkylating agent therapy.

A patient with primary plasma cell leukemia (PCL) is presented, who had an excellent response to high-dose cyclophosphamide and prolonged survival. The sole cytogenetic abnormality detected in the bone marrow was monosomy 18. Although this karyotypic aberration has been previously described in PCL, it generally occurs associated with additional abnormalities. The peripheral blood plasma cells from this patient reacted intracellularly with the monoclonal antibody OKM-1, which binds to myeloid cells at and above the level of myelocytes and to monocytes. This finding supports the idea of a common precursor cell for plasma cells and cells of the myelomonocytic lineage.

Antigens, Surface↗
PubMed1987

Prolonged evaluation of patients with corticosteroid-dependent asthma stage of allergic bronchopulmonary aspergillosis.

Eight cases with stage IV allergic bronchopulmonary aspergillosis (ABPA) (corticosteroid-dependent asthma stage) were observed for a total of 82 patient years with individual patients observed for 7 to 19 years (mean 10.2) years. One case is the first case of ABPA diagnosed in the United States in 1967. A second case has been observed through four stages of ABPA. None of these eight cases has demonstrated pulmonary deterioration by clinical, chest roentgenogram, or pulmonary function analysis. After diagnosis, the maintenance dose of prednisone in seven of eight cases was a low to moderate dose alternate-day prednisone. These results suggest that continuous observation and management of episodes of pulmonary consolidation or asthma exacerbations may prevent the progression of ABPA to stage V (fibrotic end stage). The total IgE may remain elevated in these patients, and therapy should not attempt to reduce total serum IgE to normal levels. After prolonged therapy with prednisone for asthma and control of ABPA, the IgE and IgG antibody indices against Aspergillus fumigatus may remain elevated or may be below the levels that are of diagnostic value.

Adolescent↗
PubMed1987

Philadelphia chromosome positive essential thrombocythemia evolving into lymphoid blast crisis.

The Philadelphia chromosome with the classic translocation t(9;22) was detected in all metaphases of a patient with essential thrombocythemia who presented without hematologic signs of chronic myeloid leukemia (CML). After 12 months of treatment with hydroxyurea followed by 6 months of busulfan, the disease transformed into lymphoid blast crisis with the immunophenotype of pre-pre-B cells frequently seen in lymphoid blast crisis of CML. This progression was not associated with karyotypic evolution because lymphoblasts contained only the Philadelphia chromosome. Further clinical course in this patient confirmed the development of a Philadelphia chromosome positive stem cell with predominantly megakaryocytic committment through partially megakaryocytic/lymphoid differentiation to purely lymphoid committment, a previously unreported transformation.

Adult↗
PubMed1987

Allergic bronchopulmonary candidiasis: case report and suggested diagnostic criteria.

A patient with an illness consistent with allergic bronchopulmonary candidiasis is described. The patient had asthma, atelectatic pulmonary infiltrates on three occasions, immediate cutaneous reactivity as low as 10(-7) (wt/vol) to Candida albicans extract, and precipitating antibody to this organism. C. albicans was the only organism cultured from two bronchial lavage specimens. Total serum IgE was elevated to 5745 ng/ml and decreased rapidly with corticosteroid therapy. Serologic studies were not consistent with allergic bronchopulmonary aspergillosis. Serum IgE to C. albicans, measured by ELISA after adsorption of IgG from the serum samples by incubation with staphylococcal protein A, was found to be 575% to 650% above control values. The serum IgE antibody activity against Candida decreased with clinical improvement after corticosteroid therapy.

Adolescent↗
PubMed1987

Early oral contraceptive use and breast cancer: results of another case-control study.

We report the results of a case-control study of oral contraceptive use and breast cancer conducted in London, Oxford and Edinburgh between 1980 and 1984. One thousand one hundred and twenty-five women aged 16-64 years with newly diagnosed breast cancer and a like number of matched controls were interviewed and asked about their past due use of oral contraceptives (OCs). Among women aged 45 years or more at diagnosis there was no evidence of an association between OC use and breast cancer. Among the 351 pairs of women aged under 45 years at diagnosis there was a significantly elevated risk associated with increasing duration of use before first full term pregnancy (relative risk for 4+ years use versus never use = 2.6, 95% confidence limits, 1.3-5.4). Since this result is at variance with the findings in some other studies we have investigated the nature of this association with particular emphasis on possible bias, pill type and a latent effect.

Adolescent↗