Search PubMed⌕ Search

Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 271 records · Page 15Linked to original sources
PubMed1990

Mechanisms of homologous and heterologous regulation of parathyroid hormone receptors in the rat osteosarcoma cell line UMR-106.

We have examined the mechanisms of homologous and heterologous regulation of PTH receptor binding and receptor-mediated adenylate cyclase activity in the osteosarcoma cell line UMR-106. Pretreatment with PTH resulted in a time- and dose-dependent decrease in PTH-stimulated adenylate cyclase which was maximal after 2 h and at a concentration of 10(-8) M rat (r)PTH-(1-34). PTH pretreatment over the same dose range also diminished receptor binding of 125I-labeled rPTH-(1-34); however, maximal loss of binding required 14 h and was greater than the loss of maximal adenylate cyclase activity. After 24 h pretreatment with rPTH-(1-34), cell surface receptors were decreased from 21,000 sites per cell to 2,700 sites per cell, and these down-regulated PTH receptors could not be detected in either vesicular or cytosolic subcellular fractions. Recovery from such homologous down-regulation appeared to require new receptor synthesis. Heterologous down-regulation of PTH receptors was demonstrated when UMR-106 cells were preincubated with prostaglandin E2 or (Bu)2cAMP. Heterologous desensitization was shown to be the result of a reversible modification of the PTH receptor which decreased binding affinity and decreased PTH-stimulated adenylate cyclase. Postreceptor components were also examined, and PTH but not prostaglandin E2 pretreatment was shown to decrease guanyl nucleotide binding (G) protein-mediated adenylate cyclase stimulation. This decrease in G protein function was associated with a loss of cholera toxin-catalyzed ADP ribosylation and was also detected by immunoblotting. These results indicate that PTH responses in osteoblastic cells are modulated by diverse mechanisms involving modifications both to the receptor and to postreceptor components of adenylate cyclase.

Adenosine Diphosphate Ribose↗
PubMed1990

Screening for anxiety and depression in an adolescent clinic.

The Spielberger State-Trait Anxiety Inventory (STAI) and the Children's Depression Inventory (CDI) were administered to 228 consecutive adolescent clinic patients and provisional physician diagnoses were compared with test scores obtained in 205 valid replies. The age range was 10 to 17 with a mean +/- SD of 14.3 +/- 1.8 years. Racial distribution was 176 white, 21 black, 4 Asian, and 4 other. The provisional diagnoses were categorized as follows: medical diagnosis only, 140; psychiatric diagnosis only, 45; and combined medical/psychiatric diagnosis, 20. Mean scores +/- SD for the entire study population were STAI-State 41.1 +/- 10.9, STAI-Trait 41.3 +/- 11.8, and CDI 10.1 +/- 8.3. Odds ratios showed that patients with only a psychiatric diagnosis had higher STAI scores than those with only a medical diagnosis and those with a combined medical/psychiatric diagnosis; patients with only a psychiatric diagnosis and those with a combined medical/psychiatric diagnosis had higher CDI scores than those with only a medical diagnosis. The medical records of 30 patients in the medical diagnosis category with high STAI and CDI scores were reviewed; of 140 patients with medical diagnoses, screening detected 15 patients (10.7%) who warranted further intervention for psychiatric disorders.

Adolescent↗
PubMed1990

Neutralization and delinquency: a comparison by sex and ethnicity.

A path model illustrating the relationships between church attendance, delinquent peer association, tendency to neutralize delinquency, and self-reported delinquent behavior was compared between males and females and between Mexican-American and Anglo college students (N = 694). The structure of the relationships among these variables was found to be similar across all four subsamples, although there was some variation in the strength of the relationships. In all four subsamples, the strongest paths were between neutralization and delinquent behavior, especially among Anglos and among males, and the weakest paths were between church attendance and delinquent behavior. On the other hand, church attendance was more strongly related to having fewer delinquent peers among Anglos and females. The path models explained substantial amounts of variation in delinquent behavior: 38% among Anglos, 32% among females, 31% among males, and 30% among Mexican-Americans.

Adaptation, Psychological↗
PubMed1989

Characterization of vascular smooth muscle cell phenotype in long-term culture.

Studies of bovine carotid artery smooth muscle cells, during long-term in vitro subcultivation (up to 100 population doublings), have revealed phenotypic heterogeneity among cells, as characterized by differences in proliferative behavior, cell morphology, and contractile-cytoskeletal protein profiles. In vivo, smooth muscle cells were spindle-shaped and expressed desmin and alpha-smooth muscle actin (50% of total actin) as their predominant cytoskeletal and contractile proteins. Within 24 h of culture, vimentin rather than desmin was the predominant intermediate filament protein, with little change in alpha-actin content. Upon initial subcultivation, all cells were flattened and fibroblastic in appearance with a concomitant fivefold reduction in alpha-actin content, whereas the beta and gamma nonmuscle actins predominated. In three out of four cell lines studied, fluctuations in proliferative activity were observed during the life span of the culture. These spontaneous fluctuations in proliferation were accompanied by coordinated changes in morphology and contractile-cytoskeletal protein profiles. During periods of enhanced proliferation a significant proportion of cells reverted to their original spindle-shaped morphology with a simultaneous increase in alpha-actin content (20 to 30% of total actin). These results suggest that in long-term culture smooth muscle cells undergo spontaneous modulations in cell phenotype and may serve as a useful model for studying the regulation of intracellular protein expression.

Actins↗
PubMed1989

In vitro photodynamic therapy of human lung cancer.

Photodynamic therapy (PDT) using a dihematoporphyrin ether (DHE) sensitizes malignant cells to damage by 630-nm light. This study investigated in vitro PDT sensitivity of human lung cancer cells (A549) and those factors which influence cell survival as determined by the colony formation assay. After incubation for 2, 4, or 6 hr with [DHE] of 2.5, 25, or 50 micrograms/ml, A549 received red light at dose rates of 0.27 or 0.09 mW/cm2 and energies of 0-250 mJ/cm2. Neither 630-nm light alone nor DHE alone affected cell survival. A dose rate of 0.27 mW/cm2 required less energy than 0.09 mW/cm2 for 90% cytotoxicity (180 mJ/cm2 vs 250 mJ/cm2, P less than 0.05). The energy required for 90% cytotoxicity with 25 micrograms/ml [DHE] was dependent on DHE incubation time (2 hr, 90% cytotoxicity not reached; 4 hr, 116 mJ/cm2; 6 hr, 69 mJ/cm2; P less than 0.05). In contrast, cellular [DHE] as measured by fluorescence, plateaued after 2 hr of incubation. Fluorescence microscopy revealed a time-dependent redistribution of fluorescence from the cell membrane to perinuclear and intracytoplasmic organelles. A 99% cytotoxicity required significantly less energy as [DHE] was increased (2.5 micrograms/ml, no cytotoxicity; 25 micrograms/ml, 243 mJ/cm2; 50 micrograms/ml, 111 mJ/cm2; P less than 0.05). Intracellular [DHE] was directly dependent on the incubating media [DHE] (2.5 micrograms/ml, 0.09 +/- 0.01 micrograms/10(6) cells; 25 micrograms/ml, 0.80 +/- 0.07 micrograms/10(6) cells; 50 micrograms/ml, 1.31 +/- 0.11 micrograms/10(6) cells; P less than 0.05). PDT cytotoxicity was inversely proportional to concentration of serum in the DHE media. These data illustrate that lung cancer in vitro is sensitive to PDT and is influenced by dose rate, energy input, and DHE environmental manipulations. These factors may be important in increasing the efficiency of PDT of thoracic malignancies in vivo.

Carcinoma↗
PubMed1989

Delusions and hallucinations as a reflection of the subcultural milieu among psychotic patients of the 1930s and 1980s.

Delusions and hallucinations reported in the social histories of 150 patients admitted to an East Texas state hospital during the 1930s and of 150 patients admitted during the 1980s were examined for content that would characterize and contrast the patient subcultural milieu of the two time periods. Patients admitted during the 1930s tended to reflect the material deprivation and personal powerlessness of the great depression in delusions of great wealth and positive "special powers." The hallucinatory visions and voices of the 1980s patients reflected a more threatening and negative subcultural milieu, with more visions of blood, snakes, and dead people or animals. Command hallucinations to hurt, to kill, or to do "perverse things" would also suggest that the subculture milieu of the 1980s had become more dangerous.

Adolescent↗
PubMed1989

Psychopathology in parents of depressed children and adolescents.

One hundred and seventeen biological mothers and 63 biological fathers of depressed and nondepressed, psychiatrically disturbed children and adolescents were interviewed with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. Diagnostic information was also obtained on 54 biological fathers who were unavailable for interview. Histories of depressive disorders and other forms of psychopathology were reported at high rates in the parents. Major depression was the most commonly reported disorder in interviewed parents of both sexes, but it was reported more often in mothers. Substance abuse and antisocial pathology was more prevalent in fathers. Depression in parents did not distinguish depressed from nondepressed probands, but maternal history of anxiety disorders, alcoholism and/or drug abuse, and suicidality did. Depressed probands were more likely than their nondepressed peers to have two parents with histories of depression. Mothers of younger patients had more substance abuse and suicidality in their histories than mothers of adolescents. They also reported earlier age of onset of depression and earlier age of entry into treatment.

Adolescent↗
PubMed1989

Modulation of keratin expression in type II pneumocytes by the extracellular matrix.

The expression of specific keratin intermediate filaments during differentiation of rat type II pneumocytes in primary culture on various matrices was investigated. Changes in keratin expression were assessed using a monoclonal antikeratin antibody, 24A3, known to react strongly with alveolar epithelial cells in injured lung. Type II cell differentiation was modulated by culture on extracellular matrices known to either accelerate or retard loss of differentiated morphology and metabolic function. During culture on a plastic or fibronectin-rich surface, loss of cell differentiation correlates with increased staining with 24A3 antikeratin antibody by indirect immunofluorescence and with increased abundance of a family of acidic 46,000-dalton keratin isoforms detected in two-dimensional polyacrylamide gels of type II cell cytoskeletal extracts. Loss of type II cell differentiation is retarded or prevented by culture on substrata of purified laminin or of EHS tumor-derived basement membrane (matrigel). 24A3-linked fluorescence and expression of the 46 kDa keratins are reduced in parallel, although at 7 days in culture on matrigel or laminin, keratin expression increases. The results show that changes in type II cell differentiation effected in primary culture by the extracellular matrix correlates with changes in expression of the 24A3-reactive keratins. Loss of differentiated shape and function favors expression of these cytoskeletal antigens, which may provide quantifiable markers of the type II to type I cell transition that occurs during alveolar remodeling.

Animals↗
PubMed1989

Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung.

Bleomycin causes focally diffuse interstitial fibrosis characterized by increases in the number and volume of contractile filament-laden parenchymal cells, as well as increased parenchymal contractility. However, the origin of these cells and their relationship to altered contractility, remain unknown. We now have used immunohistochemical methods to ask if cells containing smooth muscle actin and myosin are present in involved regions of parenchyma. Staining of the parenchyma of control lungs with a monoclonal antibody against alpha-smooth muscle actin is sparse, consisting of reactivity with the alveolar entrance ring (septal tip) cells as well as occasional reactivity of alveolar wall cells that may represent pericytes or contractile interstitial cells. Increased alpha-smooth muscle actin staining was observed in areas of parenchymal damage in lungs from animals sacrificed between 1 and 4 weeks postbleomycin instillation. This reactivity included altered staining of the airway and vessel smooth muscle coat as well as thickened septal tips. In addition, newly reactive cells were observed in interstitial and intraalveolar regions and in bands of thickened submesothelial tissue. Staining was most intense in the focal fibrotic lesions which are characteristic of this injury. By contrast, parenchymal reactivity with a polyclonal antibody against smooth muscle myosin at the later time points shows only a mild increase in punctate staining in the damaged foci. We hypothesize that the substantial increase in alpha-smooth muscle actin containing cells in fibrotic regions of involved parenchyma after bleomycin injury is responsible for the altered morphologic, biochemical, and mechanical properties that we have observed.

Actins↗
PubMed1989

Validity testing of commercial urine cocaine metabolite assays: I. Assay detection times, individual excretion patterns, and kinetics after cocaine administration to humans.

A validity study of eight commercial urine assays for detection of cocaine metabolite was performed on clinical specimens collected from human subjects who received single 20-mg intravenous doses of cocaine hydrochloride. The specimens were collected under controlled conditions and analyzed in random order under blind conditions. Benzoylecgonine concentration in each specimen also was determined by gas chromatography/mass spectrometry (GC/MS). Mean times of detection of the last positive specimen (greater than or equal to 300 ng/mL of benzoylecgonine equivalents) after cocaine administration varied among seven of the commercial tests from 16.9 to 52.9 h in the following ascending order: Toxi-Lab less than TDx = EMIT dau = EMIT st less than Abuscreen less than Coat-A-Count = Double Antibody. In contrast, a commercial spot test (KDI Quik Test) which was evaluated for detection of cocaine metabolite produced both false positives and false negatives for benzoylecgonine and was not considered to be a valid test for detection of cocaine metabolite. Half-lives of excretion of benzoylecgonine among four subjects varied from 5.9 to 7.9 h, and overall recovery of benzoylecgonine varied from 15.0 to 34.3% of the administered dose of cocaine.

Adult↗
PubMed1989

Validity testing of commercial urine cocaine metabolite assays: II. Sensitivity, specificity, accuracy, and confirmation by gas chromatography/mass spectrometry.

A comprehensive validity assessment study was performed on eight commercial urine assays for detection of cocaine use. Sensitivity, specificity, and accuracy of each assay were evaluated by analyzing, in random order and under blind conditions, specimens spiked with known drug concentrations and clinical specimens obtained from human subjects after intravenous cocaine use. Commercial assay results were compared with gas chromatography/mass spectrometry (GC/MS) assay of the same specimens for benzoylecgonine. All of the assays examined were determined to have utility in screening for cocaine use, with the exception of the KDI Quik Test, which was not a reliable test for detection of cocaine use. Major differences in sensitivity, specificity, and confirmation rate by GC/MS were noted among the assays, differences which should be taken into consideration when implementing a urine screening test for cocaine use or interpreting test results involving use of these assays.

Adult↗