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Biomedical subjects

C Golden

Publications and source records attributed to C Golden.

14 recordsLinked to original sources

Maternal distress, child behaviour, and disclosure of psychosocial concerns to a paediatrician.

BACKGROUND: Despite the availability of effective screening measures, primary care providers continue to fail to identify and manage many children with psychosocial problems. One of the best predictors of identification by a primary care physician is whether mothers disclose concerns about their child's psychosocial functioning to their child's physician. This study examined if maternal distress and child behaviour predicted whether mothers had and discussed concerns about their child's behaviour and emotions with paediatricians. METHODS: Participants were 138 mothers who accompanied their 4-12-year-old children to a health supervision visit at an urban teaching hospital. Mothers completed a demographic questionnaire, the Pediatric Symptom Checklist, the Beck Depression Inventory, and an exit questionnaire. Results Logistic regression correctly classified 97.3% of mothers who did not disclose child problems. Only 34.5% of mothers who did disclose were correctly classified. CONCLUSIONS: The results supported the hypothesis that mothers' psychosocial functioning is significantly related to concern about child behaviour and disclosure of concerns to the paediatrician. The inability of child behaviour and maternal functioning to predict which mothers were concerned and disclosed concerns supports the hypothesis that disclosure and identification of psychosocial problems in primary care is complex and requires a multifactor model.

Adult↗

Cell cycle regulatory gene abnormalities are important determinants of leukemogenesis and disease biology in adult acute lymphoblastic leukemia.

To test the hypothesis that cell cycle regulatory gene abnormalities are determinants of clinical outcome in adult acute lymphoblastic leukemia (ALL), we screened lymphoblasts from patients on a Southwest Oncology Group protocol for abnormalities of the genes, retinoblastoma (Rb), p53, p15(INK4B), and p16(INK4A). Aberrant expression occurred in 33 (85%) patients in the following frequencies: Rb, 51%; p16(INK4A), 41%; p53, 26%. Thirteen patients (33%) had abnormalities in 2 or more genes. Outcomes were compared in patients with 0 to 1 abnormality versus patients with multiple abnormalities. The 2 groups did not differ in a large number of clinical and laboratory characteristics. The CR rates for patients with 0 to 1 and multiple abnormalities were similar (69% and 54%, respectively). Patients with 0 to 1 abnormality had a median survival time of 25 months (n = 26; 95% CI, 13-46 months) versus 8 months (n = 13; 95% CI, 4-12 months) for those with multiple abnormalities (P <.01). Stem cells (CD34+lin-) were isolated from adult ALL bone marrows and tested for p16(INK4A) expression by immunocytochemistry. In 3 of 5 patients lymphoblasts and sorted stem cells lacked p16(INK4A) expression. In 2 other patients only 50% of sorted stem cells expressed p16(INK4A). By contrast, p16 expression was present in the CD34+ lin- compartment in 95% (median) of 9 patients whose lymphoblasts expressed p16(INK4A). Therefore, cell cycle regulatory gene abnormalities are frequently present in adult ALL lymphoblasts, and they may be important determinants of disease outcome. The presence of these abnormalities in the stem compartment suggests that they contribute to leukemogenesis. Eradication of the stem cell subset harboring these abnormalities may be important to achieve cure.

Adolescent↗

One-way cross-talk between p38(MAPK) and p42/44(MAPK). Inhibition of p38(MAPK) induces low density lipoprotein receptor expression through activation of the p42/44(MAPK) cascade.

In this paper, we report that SB202190 alone, a specific inhibitor of p38(MAPK), induces low density lipoprotein (LDL) receptor expression (6-8-fold) in a sterol-sensitive manner in HepG2 cells. Consistent with this finding, selective activation of the p38(MAPK) signaling pathway by expression of MKK6b(E), a constitutive activator of p38(MAPK), significantly reduced LDL receptor promoter activity. Expression of the p38(MAPK) alpha-isoform had a similar effect, whereas expression of the p38(MAPK) betaII-isoform had no significant effect on LDL receptor promoter activity. SB202190-dependent increase in LDL receptor expression was accompanied by induction of p42/44(MAPK), and inhibition of this pathway completely prevented SB202190-induced LDL receptor expression, suggesting that p38(MAPK) negatively regulates the p42/44(MAPK) cascade and the responses mediated by this kinase. Cross-talk between these kinases appears to be one-way because modulation of p42/44(MAPK) activity did not affect p38(MAPK) activation by a variety of stress inducers. Taken together, these findings reveal a hitherto unrecognized one-way communication that exists between p38(MAPK) and p42/44(MAPK) and provide the first evidence that through the p42/44(MAPK) signaling cascade, the p38(MAPK) alpha-isoform negatively regulates LDL receptor expression, thus representing a novel mechanism of fine tuning cellular levels of cholesterol in response to a diverse set of environmental cues.

Calcium-Calmodulin-Dependent Protein Kinases↗

Critical role of p42/44(MAPK) activation in anisomycin and hepatocyte growth factor-induced LDL receptor expression: activation of Raf-1/Mek-1/p42/44(MAPK) cascade alone is sufficient to induce LDL receptor expression.

The protein synthesis inhibitor anisomycin activates stress-related mitogen-activated protein kinases (MAPKs), namely, c-jun NH(2)-terminal kinase (p46/54(JNK)) and p38(MAPK) in mammalian cells. In this paper, we show that although exposure to anisomycin resulted in rapid and strong activation of p46/54(JNK) and p38(MAPK), with a delayed low level dual-phosphorylation of mitogen/extracellular protein kinase (p42/44(MAPK)), low density lipoprotein (LDL) receptor induction depends solely on the mild activation of p42/44(MAPK) signaling cascade in HepG2 cells. Unlike hepatocyte growth factor (HGF) which caused LDL receptor induction via rapid, strong, and Ras-dependent p42/44(MAPK) activation, anisomycin-induced p42/44(MAPK) activity and increased LDL receptor expression in a Ras-independent manner. Finally, we examined the role of the p42/44(MAPK) signaling cascade in LDL receptor induction by activating this kinase independently of anisomycin or HGF. By using estrogen-dependent human Raf-1 protein kinase in transient transfection assays, we show that the exclusive activation of the Raf-1/MEK-1/p42/44(MAPK) signaling cascade with antiestrogen ICI 182, 780 caused induction of LDL receptor expression to the same level as observed with either HGF or anisomycin. Consistent with the role of p42/44(MAPK), induction was strongly inhibited by pretreatment with the MEK-1/2 inhibitor PD98059. Our observation that anisomycin can use p42/44(MAPK) signaling cascade is a departure from established thinking, and the results presented shows that activation of the p42/44(MAPK) alone is sufficient to fully induce LDL receptor transcription.

Anisomycin↗

Acute chest syndrome and sickle cell disease.

Acute chest syndrome (ACS) is the presence of a new pulmonary infiltrate in combination with fever or respiratory symptoms in a patient with sickle cell disease. ACS is the leading cause of death in sickle cell disease, and many patients suffer from multiple, severe episodes. Age has a striking effect on the clinical course and outcome of ACS, with children having milder disease that often is infectious. Adults often have severe disease, and pulmonary fat embolism is frequently a component of severe ACS. Rapid diagnosis and appropriate therapy including antibiotics for atypical infections, fluids, aerosolized beta agonists, and adequate pain control are necessary to reduce morbidity. Transfusion is indicated in hypoxic patients and can be used to prevent recurrent episodes. As the pathophysiology of ACS is further delineated, new treatment strategies will be investigated.

Acute Disease↗

dally, a Drosophila glypican, controls cellular responses to the TGF-beta-related morphogen, Dpp.

Decapentaplegic (Dpp) is a Drosophila member of the Transforming Growth Factor-beta (TGF-beta)/Bone Morphogenetic Protein (BMP) superfamily of growth factors. Dpp serves as a classical morphogen, where concentration gradients of this secreted factor control patterning over many cell dimensions. Regulating the level of Dpp signaling is therefore critical to its function during development. One type of molecule proposed to modulate growth factor signaling at the cell surface are integral membrane proteoglycans. We show here that division abnormally delayed (dally), a Drosophila member of the glypican family of integral membrane proteoglycans is required for normal Dpp signaling during development, affecting cellular responses to this morphogen. Ectopic expression of dally+ can alter the patterning activity of Dpp, suggesting a role for dally+ in modulating Dpp signaling strength. These findings support a role for members of the glypican family in controlling TGF-beta/BMP activity in vivo by affecting signaling at the cell surface.

Animals↗

Lao Depression Inventory.

There are no measurement tools that accurately measure depression among Lao refugees. The overall purpose of this research was to complete the development and validation procedures for the Lao Depression Inventory (LDI). The study consisted of 216 Ethnic Lao refugees. A clinical interview and 164 true/false questions were administered to identify specific items which could identify depression among the Ethnic Lao people. All items were administered in both English and Lao. Overall, 78 of the 164 items differentiated groups of depressed and nondepressed Lao at the .01 level. Results of validation procedures showed that a 30-item scale had an accuracy rate of 89% in identifying the presence of depression in the validation group; the hit-rate for the same items and cutoff was 92% in the cross-validation group. Potential uses of the scale are discussed.

Depressive Disorder↗

Prosthetic usage following major lower extremity amputation.

There were 157 patients following major lower extremity amputation who were evaluated to determine functional prosthetic ambulation. Twenty-eight patients were evaluated in the amputee clinic and found not to be candidates for prosthetic fitting. Forty-one patients were fit with a prosthesis but did not become functional prosthetic ambulators. Eighty-eight patients became functional prosthetic ambulators. Of all above-the-knee amputees, 46% became functional prosthetic ambulators. Only 19% of bilateral lower extremity amputees became functional prosthetic ambulators. Of all below-the-knee amputees, 66% became functional ambulators. The presence of coronary artery disease decreased the ambulatory potential in above-the-knee or bilateral amputees but not in below-the-knee amputees. A screening method for elderly, dysvascular amputees should be instituted prior to prosthetic fitting.

Aged↗

Interactions between viruses and bacteria in patients with chronic bronchitis.

The possibility that viral infections of the respiratory tract might predispose to bacterial colonization or infection was studied in 120 patients with chronic obstructive pulmonary disease and 30 control subjects; these individuals were observed for seven years. The ratio of the number of observed to the number of expected associations between viruses and bacteria was 2.43 (P = 0.037) for the pair influenza virus and Streptococcus pneumoniae and was 2.06 (P = 0.056) for influenza virus and Haemophilus influenzae. Consistently positive, but not significant, associations were detected between rhinovirus and herpes simplex virus infections and isolations of S. pneumoniae and H. influenzae. In contrast, isolations of the nonpathogenic Haemophilus parainfluenzae could not be related to prior viral infections. Significant rises in titer of antibody to H. influenzae were detected on 76 occasions, and 20 (26%) of these antibody rises were associated with viral or mycoplasmal infections during the preceding 120 days. The expected number of such associations was 8.34 (ratio of number observed to number expected, 2.40; P = 0.08). These results suggest that viral infections of the respiratory tract in patients with chronic obstructive pulmonary disease are associated with increased colonization by potentially pathogenic bacteria and may also predispose to infections with H. influenzae.

Antibodies, Bacterial↗

Ultrasonic extraction of total particulate aromatic hydrocarbons (TpAH) from airborne particles at room temperature.

A superior enrichment procedure for the extraction of TpAH from airborne particles collected on glass fiber filter paper is described. The sample is suspended in a solvent and subjected to ultrasonic waves at room temperature with glass powder to adsorb polar coextractives. The TpAH in the filtered extracts are separated from other compounds by high speed liquid chromatography. Sensitivity is in the nanogram range, and the procedure is highly reproducible. Significantly larger amounts of TpAH are recovered than with Soxhlet extraction for 6 to 8 hours, and the percentage of pAH in the extracts is much higher. The entire procedure requires approximately 40 minutes, most of which is waiting time.

Air Pollutants↗