Biomedical subjects

J D Johnson

Publications and source records attributed to J D Johnson.

At least 73 records · Page 4Linked to original sources

PubMed1998

Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.

Highly ATP- and GTP-specific isoforms of succinyl-CoA synthetase in pigeon incorporate the same alpha-subunit, but different beta-subunits (Johnson, J. D., Muhonen, W. W., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27573-27579). The sequences of the mature subunits were determined by methods based on reverse transcription-polymerase chain reaction. The 306-residue mature alpha-subunit in pigeon shows >88% identity to its homologues in pig and rat. The sequences of the mature ATP- and GTP-specific beta-subunits (A-beta and G-beta, respectively) in pigeon are 54% identical. These sequences were used to identify expressed sequence tags for human and mouse that were highly homologous to G-beta and A-beta, respectively. The sequences for mature A-beta and G-beta in mouse and human were completed and verified by polymerase chain reaction. The sequence of A-beta in pig was also obtained. The mammalian A-beta sequences show >89% identity to each other; the G-beta sequences are similarly related. However, pairwise comparisons of the A-beta and G-beta sequences revealed <53% identity. Alignment with two sequences of the beta-subunit in Caenorhabditis elegans suggests that the A-beta and G-beta genes arose by duplication early in the evolution of multicellular eucaryotes. The expression of A-beta is strong in numerous mouse and human tissues, which suggests that ATP-specific succinyl-CoA synthetase also plays an important role in species throughout the animal kingdom.

Amino Acid Sequence↗

PubMed1998

Structural determinants of Ca2+ exchange and affinity in the C terminal of cardiac troponin C.

The C terminal of cardiac troponin C (TnC) has two Ca2+-Mg2+ sites which exhibit approximately 20-fold higher Ca2+ affinity than the two C-terminal Ca2+ specific sites in calmodulin (CaM). Substitution of the third EF-hand of TnC for the corresponding EF-hand of CaM produced a mutant (CaM[3TnC]) with a 10-fold higher C-terminal Ca2+ and Mg2+ affinity. Substitution of loop 3 of TnC for loop 3 of CaM produced a mutant (CaM[loop3TnC]) with a 10-fold faster Ca2+ on rate and a 5-fold faster Ca2+ off rate than CaM. A mutant CaM (CaM[loop3X, Z]) which contained the identical coordinating amino acids and X and Z acid pairs of TnC loop 3 had a 3-fold higher C-terminal Ca2+ affinity without the increased Ca2+ exchange rates exhibited by CaM[loop3TnC]. Thus, loop factors other than the acid pairs must be responsible for the rapid Ca2+ exchange rates of CaM[loop3TnC]. Helix 6 and helix 5 in the third EF-hand of TnC support the rapid Ca2+ on rate of TnC's loop 3 and produce an approximately 4-fold reduction in its Ca2+ off rate, explaining the high Ca2+ affinity of the third EF-hand of TnC. Exchanging loop 3 or helix 5 of TnC into CaM increased the Mg2+ affinity by decreasing the Mg2+ off rate. Our results are consistent with the high Ca2+ and Mg2+ affinity of the third EF-hand of TnC resulting from the two (X and Z) acid pairs in loop 3, coupled with the greater hydrophobicity of helix 6 and helix 5 compared to that of the third EF-hand of CaM.

Amino Acid Sequence↗

PubMed1998

Opposing roles for dopamine D1 and D2 receptors in the regulation of hypothalamic tuberoinfundibular dopamine neurons.

The purpose of the present study was to characterize pharmacologically dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons in males rats, and to determine if inhibitory dopamine D1 receptors oppose stimulatory dopamine D2 receptors and account for the inability of mixed dopamine receptor agonists to alter the activity of these neurons. Tuberoinfundibular dopamine neuronal activity was estimated by measuring the concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, the region of the hypothalamus containing terminals of these neurons. Administration of the dopamine D1 receptor agonist (+/-)-1 phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol (SKF38393) decreased median eminence DOPAC and increased plasma prolactin concentrations, whereas administration of the dopamine D1 receptor antagonist ((-)-trans,6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo[d]naphtho-[2,1 b]azepine (SCH39166) increased median eminence DOPAC concentrations but had not effect on plasma prolactin. The inhibitory effect of SKF38393 on median eminence DOPAC concentrations was blocked by SCH39166. These results demonstrate that acute activation of dopamine D1 receptors inhibits the activity of tuberoinfundibular dopamine neurons and thereby increases prolactin secretion, and that under basal conditions dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons is tonically active. Administration of the dopamine D2 receptor agonist (5aR-trans)-5,5a,6,7,8,9,9a,10-octahydro-6-propyl-pyridol[2, 3-g]quinazolin-2-amine (quinelorane) increased median eminence DOPAC concentrations, and SKF38393 caused a dose-dependent reversal of this effect. Administration of the mixed dopamine D1/D2 receptor agonist R(-)-10,11-dihydroxy-apomorphine (apomorphine) had no effect per se, but blocked quinelorane-induced increases in DOPAC concentrations in the median eminence. These results reveal that concurrent activation of dopamine D1 and D2 receptors nullifies the actions of each of these receptors on tuberoinfundibular dopamine neurons, which likely accounts for the lack of an acute effect of mixed dopamine D1/D2 receptor agonists on these hypothalamic dopamine neurons.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1998

Determinants of relaxation rate in skinned frog skeletal muscle fibers.

The influences of sarcomere uniformity and Ca2+ concentration on the kinetics of relaxation were examined in skinned frog skeletal muscle fibers induced to relax by rapid sequestration of Ca2+ by the photolysis of the Ca2+ chelator, diazo-2, at 10 degreesC. Compared with an intact fiber, diazo-2-induced relaxation exhibited a faster and shorter initial slow phase and a fast phase with a longer tail. Stabilization of the sarcomeres by repeated releases and restretches during force development increased the duration of the slow phase and slowed its kinetics. When force of contraction was decreased by lowering the Ca2+ concentration, the overall kinetics of relaxation was accelerated, with the slow phase being the most sensitive to Ca2+ concentration. Twitchlike contractions were induced by photorelease of Ca2+ from a caged Ca2+ (DM-Nitrophen), with subsequent Ca2+ sequestration by intact sarcoplasmic reticulum or Ca2+ rebinding to caged Ca2+. These twitchlike responses exhibited relaxation kinetics that were about twofold slower than those observed in intact fibers. Results suggest that the slow phase of relaxation is influenced by the degree of sarcomere homogeneity and rate of Ca2+ dissociation from thin filaments. The fast phase of relaxation is in part determined by the level of Ca2+ activation.

Acetates↗

PubMed1998

The impact of formalization, role conflict, role ambiguity, and communication quality on perceived organizational innovativeness in the Cancer Information Service.

Organizational members' levels of perceived innovativeness represent an insider's viewpoint of the organization's overall approach to innovation. This study tested a model of the impact of formalization, role ambiguity, role conflict, and communication quality on perceived organizational innovativeness in the Cancer Information Service. Data were gathered from self-report questionnaires completed by organizational members (n = 86) within the Cancer Information Service, a geographically dispersed federal government health information program that was implementing innovative intervention strategies related to disseminating health information to the public. Results indicated that although the predicted model provided a good overall fit to the data, there were some problematic paths. A revised model is offered to reconceptualize the relationships among role conflict, role ambiguity, and communication quality. These results are discussed in terms of their implications for managers and scholars who hope to understand the factors that contribute to perceptions of innovativeness in the new organizational forms emerging in the health service arena. These data suggest that formalization makes an important contribution to innovation in the highly uncertain world of new organizational forms.

Attitude of Health Personnel↗

PubMed1998

Noninvasive monitoring of fetal growth and development in the Siberian polecat (Mustela eversmanni).

The Siberian polecat (Mustela eversmanni) is the preferred species to assess procedures and establish normative values for application in the related and endangered black-footed ferret (Mustela nigripes). This study was undertaken to physically, ultrasonographically, and radiographically evaluate fetal development in a spontaneously breeding captive Siberian polecat population. Ultrasonographically, fetal sac enlargement allowed presumptive pregnancy detection as early as 12 days of gestation, the fetal pole was the first definitive sign of pregnancy at about 18 days of gestation, when the fetal heart beat also appeared, and definitive pregnancy detection by ultrasound was essentially 100% accurate after 18 days. The estimation of fetal number by ultrasound was less reliable than by radiography, as it is in other litter-bearing species. Crown-rump growth, organ differentiation, and calcification patterns resembled those of domestic carnivores except that comparable developmental stages in polecats occurred at disproportionately later times, suggesting that young Siberian polecats are delivered in a less developed state. Careful palpation permitted detection of pregnancy after day 17 but with less certainty than with ultrasound. Radiographic evaluation was insensitive and of limited value for pregnancy detection until near term. Litter number and fetal detail were difficult to assess until ossification could be observed, 3-6 days before parturition.

Animals↗

PubMed1997

Human and murine high endothelial venule cells phagocytose apoptotic leukocytes.

Apoptotic cell death occurs during normal lymphocyte development and differentiation as well as following lymphocyte exposure to endogenous corticosteroids released during stress, malnutrition, and trauma. Recognition and engulfment of these apoptotic cells is important for the clearance of dying cells before they release potent inflammatory mediators into the vasculature or tissues. Phagocytosis of apoptotic cells is accomplished in part by macrophages. We report for the first time that apoptotic lymphocytes are also phagocytosed by high endothelial venule (HEV) cells. The murine HEV cell line mHEVa rapidly phagocytosed apoptotic lymphoid and myeloid cells with the greatest rate of phagocytosis occurring at 0-6 h. To confirm HEV cell interaction with apoptotic cells, we demonstrated that apoptotic human tonsil lymphocytes were phagocytosed by human tonsil HEV cells in primary cultures. Furthermore, we examined HEV cell phagocytosis in vivo. Mice were treated with a natural corticosterone (4-pregnene-11 beta,21-diol-3,20-dione) at levels detected during stress or malnutrition (93-180 micrograms serum cortisol/dl). At 4-12 h posttreatment, apoptotic lymphocytes were present inside vacuoles of HEV cells in axillary lymph node tissue sections, as determined by transmission electron microscopy. These data suggest that, in addition to macrophages, lymph node HEV cells also play a role in the removal of apoptotic lymphocytes. Moreover, since HEV cells are specialized endothelial cells that regulate lymphocyte migration into peripheral lymphoid tissues, they may provide an important checkpoint for clearance of apoptotic lymphocytes within the vasculature, as well as limiting entrance of nonfunctional lymphocytes into the lymph node.

Animals↗

PubMed1997

Dopamine receptor-mediated regulation of expression of Fos and its related antigens (FRA) in somatostatin neurons in the hypothalamic periventricular nucleus.

Somatostatin (SS)-containing perikarya located within the hypothalamic periventricular nucleus (PeVN) comprise a heterogenous population of neurons with both local intrahypothalamic and distant extrahypothalamic axonal projection sites. The close proximity of SS perikarya and their dendrites to dopaminergic (DA) neuronal processes in the PeVN suggests that these peptidergic neurons may be regulated by DA receptor-mediated mechanisms. To test this, the effects of the D1 agonist SKF 38393 and D2/3 agonist quinelorane were examined on expression of the immediate early gene products Fos and its related antigens (FRA) in SS-immunoreactive (IR) neurons in the PeVN. SS-IR neurons were located in the most medial portion of the PeVN bordered medially by the third ventricle and laterally by tyrosine hydroxylase (TH)-IR neurons. In control rats, 10-15% of all SS-IR neurons contained FRA-IR. Activation of D1 receptors with SKF 38393 had no effect on either the total number of SS-IR neurons or the number of SS-IR neurons containing FRA-IR. In contrast, activation of D2/3 receptors with quinelorane decreased the number of SS-IR neurons containing FRA-IR, without affecting the total number of SS-IR neurons. The D2/3 antagonist raclopride had no effect per se, but prevented the quinelorane-induced decrease in the number of SS neurons expressing FRA-IR. These results reveal that activation of D2/3 (but not D1) receptors inhibits expression of the immediate early gene products FRA in SS-containing neurons in the PeVN, but expression of FRA in SS neurons is not tonically inhibited by dopamine acting on D2/3 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1997

Identification and expression of the Saccharomyces cerevisiae cytoplasmic tryptophanyl-tRNA synthetase gene.

The enzymes that aminoacylate tRNAs have been studied extensively and can be organized into two distinct classes based on signature sequences and the position of aminoacylation. The class I enzymes have canonical HIGH and KMSKS sequences as part of a Rossman fold nucleotide-binding site. The tryptophan-specific enzymes have been placed in class I based on analysis of the cognate genes from Escherichia coli, B. stearothermophilus, B. taurus, and Homo sapiens. An unidentified open reading frame (ORF) on Saccharomyces cerevisiae chromosome XV, HRE342, has 46% identity with the bovine tryptophanyl-tRNA synthetase and possesses the appropriate signature sequences. The predicted molecular weight of the putative HRE342 protein also closely matched the expected monomer size of the S. cerevisiae enzyme. The HRE342 ORF plus about 250 bp of 5' and 3' flanking sequence was amplified by polymerase chain reaction, cloned into a 2 mu based vector, and transformed into a host strain, S. cerevisiae JG369.3B. Nucleotide sequence analysis of the clone confirmed the presence of HRE342. Extracts from transformed yeast have a 30- to 100-fold increase in specific activity of the tryptophanyl-tRNA synthetase. An HRE342 locus in a diploid strain, PTY33XPTY44, was disrupted with a LEU2 insert. Sporulation and tetrad analysis of the HRE342::LEU2 strain demonstrated that HRE342 is an essential gene. We conclude that HRE342 is the S. cerevisiae gene encoding the cytoplasmic tryptophanyl-tRNA synthetase, WRS1. A search of the Saccharomyces Genome Database using amino acid sequences from other eukaryotic aminoacyl-tRNA synthetase suggests there is sufficient similarity to identify both class I and class II genes.

Amino Acid Sequence↗

PubMed1997

Functional differences among the six Saccharomyces cerevisiae tRNATrp genes.

The Saccharomyces cerevisiae haploid genome includes six copies of the gene encoding tRNATrp which are scattered on five chromosomes. Other, non-functional tDNATrp fragments also occur in the genome. The segments of all six genes which encode the 72-nucleotide mature tRNATrp, as well as a 34-nucleotide intervening sequence, are identical. However, the 5' and 3' flanking sequences diverge virtually at the boundaries of the coding region. We have used an assay based on suppression of UGA mutations by multi-copy clones of tDNATrp to search for functional differences among these genes. Previous studies with one tDNATrp had demonstrated that moderate suppression of a UGA mutation, leu2-2, resulted from introduction of a multi-copy clone of the gene. Attempts to use this assay to select tDNATrp clones from a yeast genomic library yielded only four of the six different clones. The other two genes were amplified by PCR and cloned in pRS202, a 2 mu vector also used for the genomic library. Plasmids bearing the six tRNA genes were transformed into S. cerevisiae strain JG369.3B and scored for their ability to suppress the leu2-2 mutation as well as his4-260, another UGA marker. Two of the six tRNATrp clones were unable to suppress either marker, two evidenced weak suppression of the Leu auxotrophy, and two were able to suppress both markers. Growth rates in liquid media requiring suppression were measured for cell lines carrying each of the clones. Differences greater than 50-fold were observed in media lacking histidine. An evolutionary tree based on 5'-flanking sequence corresponds reasonably well with suppressor activity, while a similar analysis of 3'-flanking sequence does not. This suggests that the functional differences are based on divergence in the 5'-flanking sequences of the tRNATrp genes.

Base Sequence↗

PubMed1997

Effects of calcium channel antagonists on Ca2+ transients in rat and canine cardiomyocytes.

First-generation Ca2+ channel antagonists depress myocardial contractility, but many of the newer Ca2+ channel blockers have a high degree of "vascular selectivity". This study compares the effects of the Ca2+ antagonists felodipine, amlodipine, mibefradil, verapamil and nifedipine, and the Ca2+ channel agonist. (S)(-)-Bay K-8644 on Ca2+ transient amplitudes in fura-2/AM-loaded rat and canine ventricular cardiomyocytes. At 10(-11) and 10(-10) M, felodipine increased [Ca2+]i transient amplitudes by 10-25% in field-stimulated fura-2-loaded cells from both species while at 10(-6) M it depressed [Ca2+]i transients by 80%. Mibefradil increased [Ca2+]i transient amplitudes by 16% at 10(-11) and 10(-10) M and decreased the transients by 25% at 10(-6) M. The calcium channel agonist, (S)(-)-Bay K-8644 increased [Ca2+]i transient amplitudes at 10(-10)-10(-6) M (maximally 37% at 10(-7) M) but depressed [Ca2+]i transients by 10% at 10(-5) M. Nifedipine was inhibitory at all concentrations tested (10(-11)-10(-6) M) in canine myocytes, but in rat cells. 10(-10) M nifedipine increased [Ca2+]i transient amplitudes by 37%. All concentrations of verapamil and amlodipine (10(-11)-10(-6) M) depressed [Ca2+]i transients in both rat and canine myocytes. We conclude that: (1) felodipine and mibefradil may be positive rather than negative inotropes at low concentrations, which are therapeutically relevant: and (2) low concentrations of nifedipine may have a positive inotropic effect in the rat but not the dog heart.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1997

The investigation of toxoplasma infection associated with pregnancy.

An audit was undertaken to determine case compliance with prenatal testing and investigation of infants for toxoplasma infection. Subsequently, the effect of enhanced reference unit Intervention was studied. The proportion of cases of toxoplasma infection associated with pregnancy completing an investigation programme was calculated. The effect of continued and short-term additional intervention was assessed and reasons for failure to comply were sought. The status of the child was established in 30% of cases when acute maternal toxoplasma infection was detected. Continuous reference unit intervention significantly improved case compliance to 45% over a 3-year period, but the effect was lost when the additional measures were withdrawn. Failure to complete the investigation procedure was associated with loss of patient-clinician contact and clinician/laboratory error. Enhanced intervention did not result in a significant improvement in compliance with the investigation programme for babies with clinical abnormality. The benefits of testing for toxoplasma infection associated with pregnancy are limited by failure to complete necessary investigations.

Adult↗

PubMed1997

A review of stress ulcer prophylaxis in the neurosurgical intensive care unit.

STRESS ULCERS OCCUR frequently in intensive care unit patients who have intracranial disease. After major physiological stress, endoscopic evidence of mucosal lesions of the gastrointestinal tract appears within 24 hours of injury; 17% of these erosions progress to clinically significant bleeding. Gastrointestinal hemorrhage has been associated with mortality rates of up to 50%. The pathogenesis of stress ulcers may not be completely understood, but gastric acid and pepsin appear to play significant roles. Antacids, H2 antagonists, and sucralfate are effective prophylactic agents in the medical/surgical intensive care unit. Appropriate therapy for neurosurgical patients remains unclear, however. This review summarizes the current literature regarding the pathogenesis and therapy of stress ulcers in neurosurgical patients.

Animals↗

PubMed1997

Recognition of tissue cyst-specific antigens in reactivating toxoplasmosis.

Current serological tests do not discriminate between asymptomatic latent Toxoplasma gondii infection and reactivating toxoplasmosis, but timely therapeutic intervention before the development of symptoms would lead to major reductions in morbidity and permanent disability. This study developed a new enzyme-linked immunosorbent assay (ELISA) for antibody to T. gondii tissue cyst antigens and screened tissue cyst antigens by Western blot analysis to test the hypothesis that antibody recognition of T. gondii tissue cyst-derived antigen is a good indicator of reactivation disease. A total of 187 sera was tested by Sabin-Feldman dye test and tissue cyst ELISA, AIDS patients and patients with ocular disease were considered separately, as the exposure to parasite antigens may be different in these two groups. The dye test did not discriminate between immunocompetent and immunocompromised T. gondii seropositive patients or between active and quiescent toxoplasmosis. Tissue cyst ELISA demonstrated a raised specific antibody response in immunocompetent T. gondii seropositive patients and in quiescent HIV positive sera. These data support th view that the tissue cyst population is in a state of dynamic equilibrium. It is proposed that, in the immunocompetent host, tissue cyst development and rupture are under some degree of immune control, but that in the immunocompromised host this equilibrium is disturbed and reactivation disease results. Data from patients with reactivating ocular toxoplasmosis demonstrate that tissue cyst-specific antibody levels are not different in active and quiescent disease and indeed they are not significantly different from immunocompetent T. gondii seronegative sera. In the Western blot analysis of 57 HIV positive patient sera, eight antigens (65, 57, 49, 47, 36, 28, 26 and 18 kDa) were consistently recognised by one third or more of the sera tested, but no single antigen was diagnostic of quiescent or active toxoplasmosis. It is concluded that tissue cyst-derived antigens are not a reliable serological marker of reactivating toxoplasmosis.

AIDS-Related Opportunistic Infections↗

PubMed1997

Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity.

LIM-homeodomain proteins direct cellular differentiation by activating transcription of cell-type-specific genes, but this activation requires cooperation with other nuclear factors. The LIM-homeodomain protein Lmx1 cooperates with the basic helix-loop-helix (bHLH) protein E47/Pan-1 to activate the insulin promoter in transfected fibroblasts. In this study, we show that two proteins originally called Lmx1 are the closely related products of two distinct vertebrate genes, Lmx1.1 and Lmx1.2. We have used yeast genetic systems to delineate the functional domains of the Lmx1 proteins and to characterize the physical interactions between Lmx1 proteins and E47/Pan-1 that produce synergistic transcriptional activation. The LIM domains of the Lmx1 proteins, and particularly the second LIM domain, mediate both specific physical interactions and transcriptional synergy with E47/Pan-1. The LIM domains of the LIM-homeodomain protein Isl-1, which cannot mediate transcriptional synergy with E47/Pan-1, do not interact with E47/Pan-1. In vitro studies demonstrate that the Lmx1.1 LIM2 domain interacts specifically with the bHLH domain of E47/Pan-1. These studies provide the basis for a model of the assembly of LIM-homeodomain-containing complexes on DNA elements that direct cell-type-restricted transcription in differentiated tissues.

Amino Acid Sequence↗

PubMed1997

Modulation of Ca2+ transients and tension by intracellular EGTA in intact frog muscle fibers.

Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) was used as an intracellular Ca2+ chelator to shorten the duration of the Ca2+ transient and to determine the rate-limiting steps in relaxation of frog skeletal muscle at 10 and 20 degrees C. Incubation with the acetoxymethyl ester of EGTA (EGTA-AM) produced a linear approximately twofold increase in the rate of fall in twitch Ca2+ concentration ([Ca2+]) over 0-70 min at 10 degrees C. The rate of relaxation initially increased from 5 to 9/s over 0-13 min and then leveled, as the rate of fall in [Ca2+] continued to increase and peak force decreased. Increasing the rate of fall in [Ca2+] increased the rate of relaxation, until a rate-limiting step was reached at approximately 9/s at 10 degrees C. At 20 degrees C, incubation with EGTA-AM produced a linear approximately twofold increase in the rate of fall in twitch [Ca2+] without affecting the rate of relaxation (27/s). Ca2+ dissociated from the regulatory sites of purified troponin (Tn) at approximately 8/s at 10 degrees C and at 23/s at 20 degrees C. When the duration of the Ca2+ transient was decreased by EGTA or increased by partial inhibition of the sarcoplasmic reticulum Ca(2+)-ATPase, twitch force increased linearly with Ca2+ transient duration. Thus the duration of the Ca2+ transient is a primary determinant of twitch force and, whereas the rate of fall in [Ca2+] is rate limiting for relaxation at 10 degrees C, Ca2+ dissociation from Tn may be rate limiting at 20 degrees C.

Animals↗

PubMed1997

Overexpression of protein tyrosine kinases in human esophageal cancer.

Using a PCR-based cloning technique, we isolated a series of protein tyrosine kinases (PTKs) expressed in a cell line of esophageal squamous cell carcinoma. Sequence analysis revealed 10 different kinds of PTKs of the receptor type [epidermal cell growth factor receptor, insulin-like growth factor I receptor, fibroblast growth factor receptor 4, eck, erk, discoidin domain receptor (DDR)/trkE/cell adhesion kinase (Cak), HEK2, HEK8, axl and sky] and one PTK of the nonreceptor type (tyk2). Subsequently, we examined the expression of the transcripts of these 11 genes in paired samples of normal and carcinomatous esophageal tissues obtained from 12 cases of esophageal cancer. We found that all 11 gene transcripts were expressed in both carcinomatous and normal tissues, and 6 of them were significantly overexpressed in carcinomatous tissues relative to adjacent normal tissues. Among these, the magnitude of mRNA expression of DDR/trkE/Cak PTK was positively correlated with the proliferative activity of carcinoma cells, but not with their degree of differentiation. Immunohistochemically, DDR was expressed in both normal and cancerous esophageal cells. The intensity of the expression was higher in cancer than normal tissue. In addition, we confirmed the expression of two isoforms of DDR/trkE/Cak in normal and cancerous esophagus. Our study suggests that DDR/trkE/Cak plays an important role in the regulation of proliferation of esophageal cancer.

Amino Acid Sequence↗

PubMed1997

Factors distinguishing regular readers of breast cancer information in magazines.

This study examined the differences between women who were regular and occasional readers of breast cancer information in magazines. Based on uses and gratifications theory and the Health Belief Model, women respondents (n = 366) were predicted to differentially expose themselves to information. A discriminant analysis showed that women who were regular readers reported greater fear, perceived vulnerability, general health concern, personal experience, and surveillance need for breast cancer-related information. The results are discussed in terms of the potential positive and negative consequences of regular exposure to breast cancer information in magazines.

Adult↗