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Biomedical subjects

J Collins

Publications and source records attributed to J Collins.

At least 325 records · Page 18Linked to original sources
PubMed1989

Monocyte superoxide secretion triggered by human IgA.

While there is much evidence for a key role of IgA in mucosal defence, its mode of action is incompletely understood. The finding of Fc receptors for IgA on various phagocytic cells has led to examination of the ability of IgA to mediate the protective functions of these cells. We studied the ability of human peripheral monocytes to secrete superoxide upon interaction with human IgA, IgG or IgM bound to a solid phase. Both secretory and serum IgA triggered the superoxide response, producing superoxide levels comparable to those induced by IgG, whereas IgM and mouse IgA were inactive. A combination of monomeric IgG and a monoclonal anti-IgG Fc receptor antibody inhibited superoxide secretion mediated through IgG but failed to block the IgA-triggered response, demonstrating that IgA was recognized through specific receptors. In addition IgA was capable of mediating phagocytosis when attached to erythrocytes.

Humans↗
PubMed1988

Alternative mechanisms for gene activation induced by poly(rI).poly(rC) and Newcastle disease virus.

After poly(rI).poly(rC) induction of FS-4 fibroblasts, both human interferon-beta (IFN-beta) mRNA and an additional induced RNA class (12S RNA) hybridize to a genomic cosmid clone containing the human IFN-beta gene as well as 35 kbp of flanking sequences. However, this coinduced 12S RNA does not originate from regions in the neighborhood of the IFN-beta gene, but hybridizes to the genomic cosmid clone via repetitive Alu-family sequences. While IFN-beta mRNA rapidly decays after reaching a maximum 2-4 h after induction, this 12S RNA is stably maintained in the fibroblast cell for more than 16 h. Contrary to IFN-beta mRNA, the level of the 12S RNA is not further elevated by superinduction conditions (cycloheximide treatment) during poly(rI).poly(rC) induction. However, subsequent to treatment with the weaker viral inducer Newcastle disease virus (NDV) both IFN-beta and the 12S RNA transcripts are induced to a higher level in the presence of cycloheximide. Cell-free translation of hybrid-selected 12S RNA leads to detection of an induced protein of 14 kDa. cDNA cloning reveals that the 12S RNA contains part of an Alu-family sequence in the 5'-untranslated region. The 12S RNA is probably not an RNA polymerase III transcript and codes for a protein of 9 kDa (as monitored by in vitro cell-free translation). This discrepancy in molecular mass can be attributed to a retarded migration of the protein in SDS/PAGE.

Amanitins↗
PubMed1988

Characterization of DNA polymerase beta mRNA: cell-cycle and growth response in cultured human cells.

DNA polymerase beta (beta-polymerase) is a housekeeping enzyme involved in DNA repair in vertebrate cells. We used a cDNA probe to study abundance of beta-polymerase mRNA in cultured human cells. The mRNA level in synchronized HeLa cells, representing different stages of the cell-cycle, varied only slightly. Contact inhibited fibroblasts AG-1522 contained the same level of mRNA as growing cells. The steady-state level of mRNA in fibroblasts is equivalent to 6 molecules per cell. The results indicate that the beta-polymerase transcript is "low abundance" and is neither cell-cycle nor growth phase responsive.

Cell Cycle↗
PubMed1988

Production of specific monoclonal antibodies against the active sites of human pancreatic secretory trypsin inhibitor variants by in vitro immunization with synthetic peptides.

Specific monoclonal antibodies against the active sites of two genetically engineered pancreatic secretory trypsin inhibitor (PSTI) variants (PSTI 0 and PSTI 4) were produced. The protease inhibitors PSTI 0 and PSTI 4 differ only by three amino acid substitution at their active sites. PSTI 0 inhibits trypsin, whereas PSTI 4 inhibits human granulocyte elastase and chymotrypsin. Immunization was performed in vitro with a synthetic heptapeptide that covers the mutated region of the protein. For this purpose in vitro culture conditions for the production of specific monoclonal antibodies against synthetic peptides were improved. The monoclonal antibodies obtained react specifically with the corresponding protease inhibitor variant. Competition experiments with trypsin and human elastase demonstrate that the protease displace the monoclonal antibody from the active site of PSTI 0 and PSTI 4 respectively.

Amino Acid Sequence↗
PubMed1988

Posttransfusion purpura associated with alloantibody specific for the platelet antigen, Pen(a).

Posttransfusion purpura (PTP) and severe thrombocytopenia occurred 9 days after transfusion of red blood cells to a 48-year-old, multiparous Navajo woman. The platelet count rose to hemostatic levels after treatment with prednisone and three plasma exchange transfusions. Serologic studies showed that the patient's serum contained the potent antibody reactive with platelets from nearly all normal subjects, but nonreactive with autologous platelets obtained after recovery. This antibody was found to be specific for a high-frequency, platelet-specific antigen, designated Pen(a),implicated previously as an immunogen in neonatal alloimmune thrombocytopenic purpura. An exchange of serum showed that Pena is identical with an alloantigen designated Yuk(b) by Japanese workers. We conclude that PTP can occur in association with alloimmunization against Pen(a) (Yuk(b).

Antibody Specificity↗
PubMed1988

An analysis of experimenter effects on responses to a sex questionnaire.

To test whether responses to sex questionnaires vary as a function of the milieu in which the questionnaires are administered, university and college students were presented with an explicit sex questionnaire by a psychologist or by a member of the clergy. In the first study conducted at a nondenominational university, students generally responded similarly when tested by a psychologist, a rabbi, or a priest. There was some evidence suggesting that a greater number of students tested by members of the clergy, rather than by the psychologist, omitted responses to sensitive questions. In a second study conducted at a Catholic college, responses generally were similar when comparing a priest and a psychologist as testers. On one sensitive item, however, there was evidence of an experimenter effect in the predicted direction. Under testing situations common to a number of studies, responses to sex questionnaires seem relatively unaffected by experimenter effects.

Clergy↗
PubMed1988

Cosmids.

Explore the source record for details and available documents.

Cloning, Molecular↗
PubMed1988

Evidence that insect embryogenesis is regulated by ecdysteroids released from yolk proteins.

That the yolk proteins (YPs), or vitellins, stored in the oocytes of insects are a nutritional store for subsequent embryogenesis has long been assumed. Exhaustive data base searching programs revealed highly significant sequence similarity between the three YPs of Drosophila melanogaster and part of the triacylglycerol lipase of the domestic pig. Based upon time of degradation of YPs during embryogenesis, existence of maternally stored ecdysteroid conjugates in embryos, location of these conjugates in locust embryos, and the fact that free active ecdysteroid hormones are released at a specific time in embryogenesis to trigger cuticle deposition, we postulate that the similarity reflects a common property of Drosophila YPs--the ability to bind the fatty acid ecdysteroid conjugates. Our finding of conjugated ecdysteroids tightly bound to purified Drosophila YP supports this prediction.

Amino Acid Sequence↗
PubMed1988

Expression of an antigen in strains of Salmonella typhimurium which reacts with antibodies to cholera toxin.

Six strains of Salmonella typhimurium (W118, TML, SL1027, LT7, M206 and Thax 1) of different virulence were examined for the presence of antigens which react with antibodies to cholera toxin (anti-CT). A fluorescent-antibody-labelling technique employing anti-CT was used to analyse antigen expression. A rapid increase in the proportion of cells producing a CT-related antigen was demonstrated in cells in early log phase (1-4 h growth) followed by a rapid decline during mid-late log phase in each of the six strains. The nature of the CT-related antigen was analysed by immunoblotting using anti-CT. An antigen of mol. wt equivalent to a high-mol. wt species of CT B subunit was detected in polymyxin-B extracts of all strains but greater amounts were observed in the strains that we consider avirulent. Nothing equivalent to a CT A-related subunit was observed in any of the strains. The relatedness of the salmonella antigen to CT was limited. The high-mol. wt antigen was not disrupted in the denaturing conditions of SDS-PAGE; nothing was detected by enzyme-linked immunosorbent assays with either ganglioside or anti-CT as anchor.

Antibodies, Bacterial↗
PubMed1988

Pharmacology and phase I/II study of continuous intravenous infusions of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme.

Forty-seven adult patients with glioblastoma multiforme (GBM) were treated in a phase I/II study combining continuous intravenous (IV) infusions of iododeoxyuridine (IdUrd) and hyperfractionated radiation therapy. IdUrd was administered as a continuous infusion (24 h/d) for two separate 14-day infusion periods. The dose of IdUrd was escalated from 500 to 1,200 mg/m2/d. The initial wide-field tumor volume was treated to 45 Gy at 1.5 Gy fractions twice daily over 3 weeks. Following a planned 2-week break, a reduced-field boost of 25 Gy was delivered using 1.25 Gy fractions twice daily over 2 weeks (total dose, 70 Gy over 9 weeks). The IdUrd infusion preceded both the wide-field and reduced-field irradiation by 1 week. All treatment was performed on an outpatient basis. Dose-limiting systemic toxicity to the bone marrow (primarily thrombocytopenia) and gastrointestinal (GI) tract (both stomatitis and diarrhea) established the maximum tolerable dose (MTD) at 1,000 mg/m2/d for a 14-day infusion. Significant local toxicity (within the radiation field) was not seen. The kinetics of IdUrd were linear with dose escalation and reached steady-state plasma concentrations of 1.3 to 3.4 mumol/L. The total body clearance of IdUrd was .82 L/min/m2. The primary metabolite, 5-iodouracil (IUra) approached steady state by day 6 of the infusion when plasma levels were 60 times higher than IdUrd. Plasma levels of uracil and thymine, but not thymidine, were elevated throughout the infusion. With a minimum follow-up of 1 year, ten patients remain alive, while 33 patients died of progressive disease, and four patients died of other causes (including one treatment-related death). The median survival for all 47 patient and for the 40 patients receiving the MTD was 45 and 47 weeks, respectively, with 12% and 14% survivals at 24 months. Using a Cox regression analysis, age (less than or equal to 50 years v greater than 50 years) and pretreatment performance status (PS) (Eastern Cooperative Oncology Group [ECOG]-PS 0 to 1 v PS 2 to 3) were independent, statistically significant (P2 less than .05) predictors of survival, with the ECOG status being a better predictor. Patients with a PS 0 to 1 (28 patients) had a median survival of 64 weeks with 21% survival at 24 months, compared with a median survival of 29 weeks and 0% survival at 12 months in the 19 patients with PS 2 to 3. The overall and subgroup survival data are at least comparable to other combined modality treatment approaches in patients with GBM.

Adult↗
PubMed1988

A comparative study of neurological and myxedematous endemic cretinism in western China.

Endemic cretinism occurs in areas of severe iodine deficiency and is manifested by two major clinical patterns, myxedematous and neurological. The relationship between these types and the factors responsible for the clinical variability are not clear. We examined 69 endemic cretins, aged 4-52 yr, categorized clinically at the beginning of the study into the three traditional types of endemic cretins, myxedematous (n = 25), neurological (n = 15), and the mixed form (n = 29), from a previously unreported endemia in Qinghai Province, China. These patients underwent detailed endocrine and neurological examination, including intelligence assessment using the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales, audiometry (in a subset of 37 patients); thyroid function testing and thyroid ultrasonography; and radiology of the skull, hand, and hip. We found that categorization of the cretins into the conventional types did not reflect the pathophysiology of the condition, since an identical pattern and intensity of neurological, intellectual, and audiometric deficits were common to and equally present in all three types of endemic cretins regardless of their thyroid function. Gait disorder (in 99%) and pyramidal signs such as patellar hyper-reflexia (in 91%) were the most common neurological abnormalities. There was no difference in mean intelligence test scores among the three groups [overall mean intelligence score (Hiskey or Griffiths tests), 28.8 +/- 12.8 (SD)]. The differing clinical manifestations of cretinism could be explained by the length and severity of thyroid hormone deficiency. Myxedematous cretins were severely thyroid hormone deficient, and as a result sexually immature, dwarfed, and had retarded skeletal maturity. They had clinical and sonographic thyroid atrophy, rather than goiter. Although neurological cretins were euthyroid, linear growth arrest lines (demonstrated radiologically) in the long bones of these cretins suggested previous hypothyroidism. Furthermore, all cretins were growth retarded when compared with peers of similar age and race. Our data therefore suggest that the different clinical types of endemic cretinism are in fact the same disorder phenotypically modified by the length and severity of postnatal hypothyroidism. The neurological manifestations are interpreted as reflecting the effects of maternal and fetal hypothyroxinemia, secondary to severe iodine deficiency, on the developing nervous system.

Adolescent↗
PubMed1988

Cerebrohepatorenal syndrome of Zellweger: a peroxisomal deficiency disorder. Case report and review.

The cerebrohepatorenal syndrome of Zellweger (CHRS) is a rare, fatal disorder in newborn infants. Recent research points to a primary absence of tissue peroxisomes, with resulting biochemical defects, as the basic pathology of the condition. We report on an infant with classic neurological and dysmorphic features of CHRS. Increased serum levels of pipecolic acid, bile acid precursors and very-long-chain fatty acids (VLCFA) together with total histological absence of liver peroxisomes confirmed the diagnosis. To our knowledge, this is the first case in Israel to be fully documented by biochemical and ultrastructural techniques. A high index of suspicion is essential among clinicians if further cases are not to be overlooked.

Facial Bones↗
PubMed1987

Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.

We investigated the peroxisomal beta-oxidation system in liver from a patient with clinical features similar to those in the cerebrohepatorenal (Zellweger) syndrome and with elevated levels in body fluids of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. The peroxisomal beta-oxidation of fatty acids, measured as the cyanide-insensitive formation of [14C]acetyl units from [14C]palmitoyl-CoA, was very low in the patient (less than 10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal beta-oxidation enzymes indicated that peroxisomal 3-oxoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16) was deficient. Addition of purified rat-liver peroxisomal 3-oxoacyl-CoA thiolase to a reaction mixture containing liver homogenate from the patient restored peroxisomal beta-oxidation. We conclude that the deficiency of peroxisomal 3-oxoacyl-CoA thiolase is responsible for the very low peroxisomal beta-oxidation activity and for the accumulation of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. Furthermore, the finding that both very-long-chain fatty acids and abnormal bile acids accumulate in this patient suggests that a single peroxisomal 3-oxoacyl-CoA thiolase is involved in the oxidative chain shortening of both very-long-chain fatty acids and the coprostanoic acids.

Acetyl-CoA C-Acyltransferase↗
PubMed1987

Effect of hemolysis on apparent values of platelet-associated IgG.

Addition of red blood cells hemolyzed in the presence of dilute plasma in quantities equivalent to as little as 0.2% hemolysis of red blood cells in whole blood caused significant elevation in the apparent value of IgG associated with platelets (PAIgG) isolated from the preparation. Addition of hemolysate to plasma containing low concentrations of platelets, simulating that obtained from thrombocytopenic patients, caused more striking elevations in apparent PAIgG. Centrifugation of platelet-rich plasma containing hemolysate through a 30% solution of Percoll restored the value of PAIgG essentially to normal. Additional studies using simulated patient whole blood samples anticoagulated with EDTA yielded similar results. The apparent elevation of PAIgG in these preparations appears to result from IgG-bearing membranous material and microspherocytes that co-isolate with platelets separated from blood by conventional methods. Caution should be used in interpreting the results of PAIgG measurements on platelets isolated from blood samples in which even minimal in vitro hemolysis has occurred.

Blood Platelets↗
PubMed1987

Halogenated pyrimidines as radiosensitizers in the treatment of glioblastoma multiforme.

Sixty patients with high-grade gliomas (including 50 patients with glioblastoma multiforme) were entered on four sequential Phase I trials combining continuous intravenous infusions of halogenated pyrimidines and high-dose brain irradiation. Patients received two 14-day infusions of bromodeoxyuridine (BUdR) or iododeoxyuridine (IUdR) during the initial wide field and later reduced field radiation treatment (total radiation dose 65-70 Gy). All patients were followed a minimum of 6 months or until death. The actuarial median survival was 13 months for the entire group, with an 18-month survival of 24%. No significant survival differences were observed based on BUdR versus IUdR, 12-h versus 24-h infusion schedule, degree of surgical resection, or sex. Good performance status and age under 50 years were significant favorable prognostic factors. Of interest, the 48 patients who completed planned treatment had a 14-month median survival, with a 30% 18-month survival. These survival observations are at least comparable to other combined modality trials in patients with glioblastoma multiforme. Ongoing and planned clinical trials using the halogenated pyrimidine analogs as radiosensitizers in patients with glioblastoma multiforme are discussed.

Astrocytoma↗
PubMed1987

Use of immobilized platelet membrane glycoproteins for the detection of platelet-specific alloantibodies in solid-phase ELISA.

Platelet membrane glycoproteins were isolated from intact platelets by detergent-phase extraction, fixed to the wells of microtiter trays and used as targets for the detection of platelet-reactive alloantibodies by enzymelinked immunospecific assay (ELISA). The final preparations contained 0.4% of total platelet protein. Antibodies reactive with antigens PlA1, PlA2, Baka, Pena and HLA-A2 were specifically detected at dilutions ranging form 1:640 to 1:1.600. Under the conditions utilized, the ELISA was more sensitive than assays involving 51Cr, radiolabeled monoclonal anti-IgG binding, and indirect immunofluorescence testing by one order of magnitude or greater. When platelets were pretreated with chloroquine to remove class I HLA antigens prior to detergent-phase extraction, reactions with HLA-specific antibodies were lost, but reactions with platelet-specific alloantibodies were retained. This approach offers a simple, sensitive and rapid method to detect and identify platelet-specific alloantibodies in sera containing HLA-reactive alloantibodies.

Antibodies↗