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Biomedical subjects

J McLaughlin

Publications and source records attributed to J McLaughlin.

At least 127 records · Page 7Linked to original sources
PubMed1988

The effects of chronic otitis media on motor performance in 5- and 6-year-old children.

Two 16-member groups of 5- and 6-year-old children, one group with a history of chronic otitis media and one without such a history, were tested on three measures of motor performance. These were the Motor Accuracy Test-Revised, the Stott Test of Motor Impairment, and measures of duration of standing balance. These instruments assess, respectively, fine motor coordination, overall motor skills, and balance. On each of these measures, children with a history of chronic otitis media scored lower than children without such a history. However, when these scores were compared statistically, no significant differences were found between the two groups. Because the results of this study were inconclusive, routine motor performance evaluation of children with a history of chronic otitis media is not advocated at this time.

Child↗
PubMed1988

Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study.

Lipocortins, a group of corticosteroid-induced phospholipase-inhibitory proteins, are thought to play a prominent role in the mediation of the anti-inflammatory effects of steroids. The synthesis and release of these proteins may represent a major endogenous mechanism of regulation of extracellular phospholipase A2 (PLA2) activity. Because soluble PLA2 activity has been associated with circulatory collapse in hyperphospholipasemic conditions, such as septic shock and pancreatitis, we examined the relationship between circulating PLA2 activity and adrenocortical function. In a prospective study of 10 episodes of septic shock, serum PLA2 and cortisol levels correlated significantly in all survivors (p less than 0.0001), whereas such a correlation was absent in all nonsurvivors (p less than 0.07). No significant correlation of cortisol and adrenocorticotropic hormone (ACTH), or PLA2 and ACTH, was found in any patient, suggesting that the stimulus for cortisol release arises from outside the hypothalamic-pituitary axis. These data suggest that, in human beings, the regulation of soluble PLA2 activity may be mediated by adrenocortical hormones, perhaps through the intermediary action of lipocortins.

Adrenocorticotropic Hormone↗
PubMed1987

The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts.

The v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) is known to efficiently transform NIH/3T3 fibroblasts in vitro and to cause an acute lymphosarcoma in susceptible murine hosts. The role of its relative, the bcr/abl gene product, in the etiology of human chronic myelogenous leukemia (CML) remains speculative. To assess the transforming properties of the bcr/abl gene product, complementary DNA clones encoding the CML-specific P210 bcr/abl protein were expressed in NIH/3T3 fibroblasts. In contrast to the v-abl oncogene product P160, the P210 bcr/abl gene product did not transform NIH/3T3 cells. Cell lines were isolated that expressed high levels of the P210 bcr/abl protein but were morphologically normal. During the course of these experiments, a transforming recombinant of bcr/abl was isolated which fuses gag determinants derived from helper virus to the NH2-terminus of the bcr/abl protein. This suggests that a property of viral gag sequences, probably myristylation-dependent membrane localization, must be provided to bcr/abl for it to transform fibroblasts.

Abelson murine leukemia virus↗
PubMed1987

Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL.

In the Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML), the c-abl gene on chromosome 9 is translocated to bcr on chromosome 22. This results in the expression of a chimeric bcr-abl message that encodes the P210bcr-abl tyrosine kinase. The cells of 10% of acute lymphocytic leukemia patients (ALL) carry a cytogenetically similar Ph1 translocation. We report that Ph1-positive ALL cells express unique abl-derived tyrosine kinases of 185 and 180 kilodaltons that are distinct from the bcr-abl-derived P210 protein of CML. The appearance of the 185/180-kilodalton proteins correlates with the expression of a novel 6.5-kilobase messenger RNA. Thus, similar genetic translocations in two different leukemias result in the expression of distinct c-abl-derived products.

DNA, Neoplasm↗
PubMed1987

Molecular cloning and serological characterization of an altered c-abl gene product produced in Ph1 CML patients.

The reciprocal translocation between human chromosomes 9 and 22, termed the Philadelphia chromosome (Ph1), is observed in more than 90% of patients with chronic myelogenous leukemia. This translocation fuses sequences from a variable distance 5' to the c-abl locus on chromosome 9 to sequences in a breakpoint cluster region (bcr) on chromosome 22. The appearance of the Ph1 chromosome is correlated with the production of a novel 8.7-kb RNA transcript containing both bcr and c-abl sequences as well as with a 210-kd phosphoprotein (p210c-abl) representing non-abl polypeptide sequences fused to c-abl-derived sequences. Antibodies prepared to a number of different c-abl domains and to bcr determinants were employed to characterize the normal and altered c-abl gene products. By combining a variety of cDNA cloning techniques, we have isolated bcr/abl clones representing 8.7 kb of contiguous mRNA sequence.

Cloning, Molecular↗
PubMed1987

Trypanosoma rhodesiense: antigenicity and immunogenicity of flagellar pocket membrane components.

A low density membrane fraction, isolated from the bloodstream stage of Trypanosoma rhodesiense and enriched in flagellar pocket membrane, was characterized with regard to antigenicity using antibodies raised against purified flagellar pocket membrane. Mild trypsinolysis of flagellar pocket membrane released two small peptides (Mr = 13-16 X 10(3)) separated by chromatofocusing (pI = 6.8 and 5.8) that were antigenic as monitored by fused rocket immunoelectrophoresis. Both of these antigenic peptides were enriched in relative fluorescence when flagellar pocket membrane was prepared from surface labeled (fluorescamine-beta-cyclodextrin) trypanosomes, indicating that cleaved peptides were on the external (luminal) side of the flagellar pocket membrane. More extensive release of fluorescamine labeled flagellar pocket membrane components was affected using mild detergent treatment (0.15% Zwittergent 3-12/0.4% Triton X-100), crossed immunoelectrophoresis separating two prominent antigens was more pronounced after incubation of flagellar pocket membrane with either porcine pancreas phospholipase A2 or umbilical cord sphingomyelinase. The use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent electroblotting to nitrocellulose also revealed two principal flagellar pocket membrane antigens (Mr approximately 60 and 66 X 10(3)), the latter showing greater release after exposure to sphingomyelinase or phospholipase, compared to mild detergent or 50 mM acetate, pH 5.0. Both antigens were glycoprotein as judged by electroblotting and the use of concanavalin A conjugated horseradish peroxidase as probe. Neither flagellar pocket membrane antigen was found to react with monoclonal antibodies prepared against T. rhodesiense variable surface antigen. The use of flagellar pocket membrane in the presence of Freund's complete adjuvant was found to protect mice against challenge infections with either the CP344 clone or uncloned CT Well-come isolate of T. rhodesiense.

Animals↗
PubMed1987

Prevalence of abnormalities found by sinus x-rays in childhood asthma: lack of relation to severity of asthma.

We examined the prevalence of abnormalities found by sinus x-rays in patients with asthma. The overall prevalence of abnormalities found was greater in the patients with asthma, 43 of 138 (31.2%), compared to control patients with dental problems, 0 of 50 (p less than 0.001). However, the percent of patients with abnormalities found by sinus x-rays was the same whether the asthma was mild, requiring minimal medication, or severe, requiring multiple medications. The results provide no support for the hypothesis that sinusitis, as detected by abnormalities found by sinus x-rays, aggravates asthma and promotes increased need for medication to control the asthma.

Allergens↗
PubMed1987

In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome.

The Philadelphia chromosome [t(9;22)-(q34;q11)] is the cytogenetic hallmark of human chronic myelogenous leukemia. RNA splicing joins sequences from a gene on chromosome 22 (BCR) across the translocation breakpoint to a portion of the ABL oncogene from chromosome 9, resulting in a chimeric protein (P210) that is an active tyrosine kinase. Although strongly correlated with this specific human neoplasm, and implicated as an oncogene by analogy to the gene product of the Abelson murine leukemia virus, the P210 gene had not been tested directly for oncogenic potential in hematopoietic cells. We have used a retroviral gene-transfer system to express P210 in mouse bone marrow cells. When infected bone marrow is plated under conditions for long-term culture of cells of the B-lymphoid lineage, cells expressing high amounts of P210 tyrosine kinase dominate the culture and rapidly lead to clonal outgrowths of immature lymphoid cells. Expression of P210 is growth-stimulatory but not sufficient for full oncogenic behavior. Some clonal lines progress toward a fully malignant phenotype as judged by increased cloning efficiency in agar suspension and frequency and rapidity of tumor induction in syngeneic mice. Such in vitro systems should be useful in evaluating the sequential and perhaps synergistic involvement of the P210 gene and other oncogenes as models for the progressive changes observed in human chronic myelogenous leukemia.

Animals↗
PubMed1986

The association of distinct acid phosphatases with the flagella pocket and surface membrane fractions obtained from bloodstream forms of Trypanosoma rhodesiense.

Cell fractionation of bloodstream Trypanosoma rhodesiense, using isopycnic sucrose gradient centrifugation, reveals acid phosphatase activities against a range of substrates to be associated, to varying degrees, with subcellular particle populations identified as derived from flagella pocket membrane and surface membrane. Using these same substrates (alpha and beta glycerophosphate, p-nitrophenyl phosphate and glucose-6-phosphate) at least two distinct acid phosphatase activities can be distinguished. One is thermolabile (approximately 80% inactivated after 30 min. at 60 degrees C), sensitive to tartrate (50% inhibited at 1.8 mM Na tartrate) with a pH optimum approximately 4.5 and appears to exhibit little substrate preference. The other acid phosphatase is relatively heat stable (approximately 30% inactivated), insensitive to tartrate (greater than 5.0% inhibited using 1.8 mM Na tartrate) exhibits a somewhat higher pH optimum (approximately 6.0) and is more substrate specific (6X more active toward glucose-6-PO4 than beta-glycerophosphate). Further cell fractionation experiments reveal 85% of the tartrate sensitive acid phosphatase to be associated with flagella pocket membrane and to account for 80% of the organisms hydrolytic activity toward beta-glycerophosphate. The tartrate resistant acid phosphatase however, has a much less exclusive localization being almost equally distributed between surface membrane (40%) and flagella pocket membrane (60%).

Acid Phosphatase↗
PubMed1986

Emergency pediatric tracheostomy: a usable technique and model for instruction.

Tracheostomies, although rarely performed, may be necessary in cases in which a cricothyrotomy is precluded by the small size of the cricothyroid space in infants and small children, when there is a high-grade upper airway obstruction, or when massive neck swelling or laryngeal fractures obscure the cricothyroid landmarks. A new technique for emergency pediatric tracheostomy and a model for practicing the procedure in cats has been developed. The technique uses a finder needle and a saline-filled syringe to locate the small and poorly defined trachea. Free-flowing saline or aspirated air bubbles indicate entrance of the locator needle into the tracheal lumen. A stabbing incision is made lateral to and against the needle, the stoma is spread, and an endotracheal tube is introduced. Kittens weighing 1,000 g to 1,500 g have a tracheal diameter of 5.5 mm to 6.0 mm, equivalent to a child less than 1 year old. Cats in the 2,000-g to 3,000-g range approximate the tracheal size for an older child. Either recently killed or anesthetized cats may be used. Using this model, emergency physicians can become more proficient in performing tracheostomies rapidly on small subjects. This technique, however, has not been studied in human beings of the pediatric age group.

Animals↗
PubMed1986

Variable expression of the translocated c-abl oncogene in Philadelphia-chromosome-positive B-lymphoid cell lines from chronic myelogenous leukemia patients.

The consistent cytogenetic translocation of chronic myelogenous leukemia (the Philadelphia chromosome, Ph1) has been observed in cells of multiple hematopoietic lineages. This translocation creates a chimeric gene composed of breakpoint-cluster-region (bcr) sequences from chromosome 22 fused to a portion of the abl oncogene on chromosome 9. The resulting gene product (P210c-abl) resembles the transforming protein of the Abelson murine leukemia virus in its structure and tyrosine kinase activity. P210c-abl is expressed in Ph1-positive cell lines of myeloid lineage and in clinical specimens with myeloid predominance. We show here that Epstein-Barr virus-transformed B-lymphocyte lines that retain Ph1 can express P210c-abl. The level of expression in these B-cell lines is generally lower and more variable than that observed for myeloid lines. Protein expression is not related to amplification of the abl gene but to variation in the level of bcr-abl mRNA produced from a single Ph1 template.

B-Lymphocytes↗
PubMed1986

Overlapping cDNA clones define the complete coding region for the P210c-abl gene product associated with chronic myelogenous leukemia cells containing the Philadelphia chromosome.

The Philadelphia chromosome, observed in greater than 90% of patients with chronic myelogenous leukemia, results from a reciprocal translocation between chromosomes 9 and 22. The translocation breakpoint on chromosome 9 occurs near the ABL gene and correlates with the production of a chronic myelogenous leukemia-specific 8.5-kilobase ABL-related mRNA species accompanied by a structurally altered ABL protein (P210c-abl). The N-terminal sequence of the protein is derived from the BCR gene on chromosome 22. We have isolated overlapping cDNA clones from the K-562 cell line corresponding to approximately 8.5 kilobases of mRNA and have sequenced 2550 nucleotides at the 5' end. Our results indicate that the 5' end of the 8.5-kilobase mRNA consists of greater than 400 nucleotides of noncoding sequence that are greater than 80% G + C rich. Based on our sequence analysis, we propose that initiation of translation occurs at nucleotide 471, such that the initial 927 amino acids of P210c-abl are derived from BCR sequences. Our cDNA clones thus define the complete coding sequences for the P210c-abl gene product.

Base Sequence↗
PubMed1986

Adrenocortical dysfunction in acute medical illness.

To further characterize the adrenocortical response to acute illness, we measured basal and adrenocorticotropic hormone (ACTH)-stimulated 11-deoxycortisol, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). Acutely ill patients had higher ACTH-stimulated 11-deoxycortisol and androstenedione, and decreased basal and ACTH-stimulated androstenedione/cortisol and DHEAS/cortisol ratios. Our data suggest that a shift away from androgen synthesis toward the glucocorticoid pathway occurs in acute illness.

Acute Disease↗
PubMed1986

Acute myocardial infarction among Navajo Indians, 1976-83.

We found that from 1976 through 1983 the incidence of acute myocardial infarction (AMI) diagnosed among Navajo Indians remained low (0.5 per 1,000 persons age 30 years or more), although the incidence in women appears to be climbing. Navajo AMI patients are more likely to be hypertensive and diabetic than age- and sex-matched patients with gallbladder disease. Twenty-four per cent die within one month of AMI.

Adolescent↗
PubMed1985

The presence of alpha-glycerophosphate dehydrogenase (NAD+-linked) and adenylate kinase as core and integral membrane enzymes respectively in the glycosomes of Trypanosoma rhodesiense.

A subcellular fraction enriched 12 times in glycosomes (NAD+-linked alpha-glycerophosphate dehydrogenase) and devoid of detectable contamination from other subcellular components, was prepared from bloodstream Trypanosoma rhodesiense. Using a method employing exposure to toluene as a means of studying normally latent glycosomal enzymes, and phospholipase A2 as a membrane probe, the association of adenylate kinase and alpha-glycerophosphate dehydrogenase with the glycosome was studied. The normally latent glycerophosphate dehydrogenase (NAD+ linked), it is proposed, is an intraglycosomal enzyme having no membrane association, but bound to the core by weak ionic linkages. As such it is possible to release the enzyme from permeable (toluene treated) glycosomes using Cl-, with a resulting 4-fold increase in the Km for dihydroxyacetone phosphate. The presence of Cl- also stimulates an increase in specific activity, but this is observed before any release of enzyme. In contrast adenylate kinase, a non-latent glycosomal enzyme, is clearly membrane associated, the use of phospholipase A2 revealing an absolute dependence on phospholipid for activity. Restoration of activity appears to specifically require phosphatidyl choline and to be co-operative in nature (nH = 1.56). It is proposed that adenylate kinase is an integral glycosomal membrane enzyme, probably affecting the control of intra-glycosomal ADP/ATP levels.

Adenylate Kinase↗
PubMed1985

A high affinity Ca2+-dependent ATPase in the surface membrane of the bloodstream stage of Trypanosoma rhodesiense.

Addition of Ca2+ (0.01-1 mM) to a standard Trypanosoma rhodesiense Mg2+-ATPase assay failed to elicit any increase in activity. However, in the absence of externally added Mg2+ and using calcium-EGTA or calcium-CDTA to precisely maintain free metal ion concentration, it was possible to measure a specific Ca2+-ATPase. Cell fractionation studies revealed this ATPase to be predominantly associated with subcellular particles having an equilibrium density of 1.22 g cm-3 and identified as surface membrane. Using a discontinuous sucrose gradient, a surface membrane enriched (SME) fraction, only slightly contaminated with mitochondria as judged by dichlorophenolindophenol-linked alpha-glycerophosphate dehydrogenase activity, was prepared. The SME fraction exhibited Ca2+-ATPase activity, using 200 nM free Ca2+, of 90 and 21 mU mg-1 protein, respectively, using CDTA and EGTA as buffering ligands. This latter result was most unexpected and indicated that the Ca2+-ATPase, in addition to having no Mg2+ requirement, was inhibited by submicromolar levels of Mg2+. The Ca2+-ATPase was found to have a K0.5 = 128 +/- 22 nM free Ca2+, the response to increasing Ca2+ concentration displaying an extremely high degree of co-operativity (Hill number (nH) = 4.9). The enzyme was found to be highly substrate-specific for ATP with K0.5 = 6.2 +/- 0.61 microM ATP. A Hill plot of the reaction velocity as a function of ATP concentration indicated two substrate binding sites (nH = 1.55). A range of potential modulators of ATPase activity were investigated, with only vanadate (V2O3-8) having any effect: 47% inhibition at 5.0 microM. The Ca2+-ATPase was unaffected by the calmodulin antagonists chlorpromazine (50 microM) and trifluoperazine (50 microM), whilst addition of calmodulin failed to produce any stimulation of activity. It is concluded that the kinetic properties of this ATPase are compatible with a potential role in the regulation of intracellular Ca2+ in bloodstream T. rhodesiense.

Adenosine Triphosphatases↗
PubMed1985

The self-care behavior inventory: a model for behavioral instrument development.

The Self-Care Behavior (SCB) Inventory was developed as part of a long-term study of self-care practices of persons who have multiple sclerosis (MS) in Denmark. The universe of behaviors regarding the physical, social, emotional, environmental, and spiritual aspects of coping with the illness was ascertained by informal and formal interviews. Respondents were asked not only what behavior was performed, but also who performed it, how it was performed, why, when, and where it was performed, and where the knowledge to perform the behavior in this manner was acquired, such as a lay-referral network, physician, social worker, spouse, or media. The inventory went through a series of drafts and pre-tests, resulting in a final version that met criteria for validity and reliability. The model presented for the development of the SCB Inventory can be useful for designing behavioral inventories and assessment tools for other chronic conditions such as arthritis, epilepsy, and diabetes.

Data Collection↗