Decreased nasal goblet cells in patients reporting topical corticosteroid use.
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Adrenal Cortex Hormones↗
Biomedical subjects
M Lee
Publications and source records attributed to M Lee.
The effect of division of the transverse carpal ligament on flexor tendon excursion.
The effect of the transverse carpal ligament (TCL) as a pulley was evaluated by measuring flexor tendon excursion after ligament division and by changing wrist position through a range of flexion and extension. Eight fresh cadaver upper extremities were mounted in a device and tendon excursions from full extension to fingertip-palm contact were measured for each flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendon. Measurements were performed with the wrist at 30 degrees extension, neutral, 30 degrees flexion, and 60 degrees flexion. The TCL was then sectioned, the skin was sutured, and the measurements were repeated. Two forms of carpal ligament repair were then done--transposition flap and aponeurotic repairs--and measurements were again repeated. With increasing wrist flexion, greater excursion differences were noted. Analysis of variance revealed that for both FDS and FDP, a significant difference in excursion occurred at 60 degrees wrist flexion and 30 degrees wrist extension with no ligament reconstruction or aponeurotic repair, compared to values prior to carpal tunnel release (p < .05) and to transposition ligament repair (p < .05).
Cadaver↗
The optimal duration of adjuvant tamoxifen treatment for breast cancer remains uncertain: randomize into aTTom.
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Antineoplastic Agents, Hormonal↗
Structure-activity relationship of a series of C-terminus modified aminoalkyl, diaminoalkyl- and anilino-containing analogues of the benzoic acid mustard distamycin derivative tallimustine: synthesis, DNA binding and cytotoxicity studies.
As part of our investigations into the design of more cytotoxic analogues of the experimental anticancer drug tallimustine, 1, C-terminus modified aminoalkyl-, 2a-c, diaminoalkyl-, 3, and anilino-containing, 4, derivatives have been synthesized. Compounds 2a-c differ by 2, 3, or 4 methylene units in the C-terminus, respectively. Results from an ethidium displacement study on poly(dA-dT), poly(dG-dC), calf thymus DNA and T4 coliphage DNA showed that compounds 2-4 interact in the minor groove of the polynucleotides with a preference for poly(dA-dT) over poly(dG-dC). Compound 4 bound more weakly to the DNAs than 2a-c and 3. Using a CD dilution assay compounds 2a-c and 3 were demonstrated to bind irreversibly to calf thymus DNA. The sequence selectivity by which compounds 2-4 alkylate DNA was demonstrated using a Taq polymerase stop assay. All the compounds alkylated preferentially at the 3'-purine residue in a 5'-TTTTGPu-3' sequence (Pu = A or G). This observed sequence specificity is similar to that of tallimustine and a related compound 5. At an equimolar concentration the aminoalkyl compounds 2a-c (2b > 2a > 2c), and diaminoalkyl compound 3 were more efficient at alkylating these sequences than the anilino compound 4. Following a one hour exposure of human chronic myeloid leukemia K562 cells, compounds 2b and 3 have lower IC50 values (1.64 microM and 3.03 microM, respectively) than tallimustine (5 microM) and similar values to a related compound 5 (2.2 microM). The order of cytotoxicity for all the compounds is 2b > 5 > 3 > 2a > 1 > 2c = 4. These results indicate that the cytotoxicities of these compounds are related to their relative ability to alkylate the consensus DNA binding sequence.
Alkylation↗
A new type of carboxypeptidase A inhibitors designed using an imidazole as a zinc coordinating ligand.
2-(4-Imidazoyl)hydrocinnamic acid (1) and its congeners (2-4) having different length of alkyl chain spacers between the imidazole ring and the alpha-carbon to the carboxylate of 1 have been designed, synthesized and evaluated as inhibitors for carboxypeptidase A to show that they are competitive inhibitors for the enzyme. Inhibitor 1 was most potent having the Ki value of 0.8 microM. The present study demonstrates that imidazole ring is an effective zinc coordinating ligand that can be useful for the design of inhibitors for zinc proteases.
Carboxypeptidases↗
Parasuicide, depression and the anticipation of positive and negative future experiences.
BACKGROUND: Previous research has shown that parasuicides' view of the future is characterized by an absence of anticipation of positive experiences rather than the presence of anticipation of negative experiences. The present study aimed to replicate this finding and examine whether it would also be found in parasuicides who were not depressed. METHOD: Depressed parasuicides (N = 27), non-depressed parasuicides (N = 17) and matched controls (N = 34) were assessed on their anticipation of future positive and negative experiences using an adapted fluency paradigm, where they were given a set time to generate future positive and negative anticipated experiences. RESULTS: Consistent with previous findings, parasuicides showed an overall reduced anticipation of positive experiences and no overall increased anticipation of negative experiences. However, the parasuicides did show evidence of increased negative anticipation for the immediate future. The results for depressed and non-depressed parasuicides were essentially the same. CONCLUSION: Lack of positive anticipation in the absence of increased negative anticipation is a feature of parasuicide. Although this lack of positive anticipation can occur in depression, it appears to be an independent feature of parasuicide.
Adult↗
Dietary and tobacco risk factors for adult onset glioma in the San Francisco Bay Area (California, USA)
The roles of diet and tobacco in the etiology of primary brain cancer are controversial. In this report, we compare dietary and cigarette smoking histories among 434 adults newly diagnosed with glioma in the San Francisco Bay Area (California, USA) between 1991 and 1994 with frequency age, gender, and ethnicity-matched population-based controls. Data were obtained on use of vitamin supplements and mean weekly consumption of each of 24 food groups. Adjusted for age, family income, and education, for both men and women, cases had higher mean weekly consumption of cured meats and other cured foods, lower consumption of high vitamin A and C fruits and vegetables, and higher average intakes of beer and other alcohol than controls. Men with brain cancer were twice as likely as control men to report high consumption of cured foods and low consumption of foods rich in vitamin C (odds ratio [OR] = 2.0, 95 percent confidence interval [CI] = 1.2-3.5). This association was less pronounced and not statistically significant in women (OR = 1.5, CI = 0.8-2.7). Similarly, men with brain cancer were twice as likely as controls to have high nitrite and low vitamin C consumption. Among men only, cases were 1.8 times more likely than controls to report smoking unfiltered cigarettes (CI = 0.9-3.4). Moreover, among smokers cases smoked unfiltered cigarettes almost twice as long as controls (P = 0.04) and cases' average total pack-years also significantly exceeded controls. Although these findings support the hypothesis that N-nitroso compounds might be a factor in adult glioma, they are compatible with other dietary hypotheses. In particular, these results also favor the hypothesis that total body burden of oxidants may play a role in brain cancer causation.
Adult↗
The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.
The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.
Adult↗
Aspirin, but not sodium salicylate, indomethacin, or nabumetone, reversibly suppresses 1,2-dimethylhydrazine-induced colonic aberrant crypt foci in rats.
The aim of this study was to determine if selective inhibition of cyclooxygenase isozymes affects the initiation of carcinogen-induced colon cancer using aberrant crypt foci (ACF) as a surrogate biomarker. Male Sprague-Dawley rats (18 per group) were given single subcutaneous injections of saline (4 ml/kg), aspirin (50 mg/kg body wt) sodium salicylate (50 mg/kg), indomethacin (4 mg/kg), nabumetone (100 mg/kg), or 16,16-dimethyl-prostaglandin E2 (50 mg/kg) for three days. On day 4, 12 rats per group were given a subcutaneous injection of 1,2-dimethylhydrazine (12 mg base/kg body wt) and six rats per group received vehicle alone (4 ml/kg) every week for eight weeks, after which drug treatment ceased. Control and six carcinogen-treated rats per group were killed at this time and the remaining six rats per group killed 22 weeks later. Colons were scored for ACF number and size. Only aspirin caused a significant reduction in total ACF and ACF formation at the early time point, but at the later time, there were no significant differences between groups. ACF from all treatment groups increased in size at similar rates at both time points. Thus, only aspirin demonstrated a significant, although reversible, suppression of carcinogen-induced ACF. Possible mechanisms of action and the clinical implications of aspirin chemoprevention are discussed.
1,2-Dimethylhydrazine↗
Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice.
The mechanism by which mutations in the presenilin (PS) genes cause the most aggressive form of early-onset Alzheimer's disease (AD) is unknown, but fibroblasts from mutation carriers secrete increased levels of the amyloidogenic A beta 42 peptide, the main component of AD plaques. We established transfected cell and transgenic mouse models that coexpress human PS and amyloid beta-protein precursor (APP) genes and analyzed quantitatively the effects of PS expression on APP processing. In both models, expression of wild-type PS genes did not alter APP levels, alpha- and beta-secretase activity and A beta production. In the transfected cells, PS1 and PS2 mutations caused a highly significant increase in A beta 42 secretion in all mutant clones. Likewise, mutant but not wildtype PS1 transgenic mice showed significant overproduction of A beta 42 in the brain, and this effect was detectable as early as 2-4 months of age. Different PS mutations had differential effects on A beta generation. The extent of A beta 42 increase did not correlate with presenilin expression levels. Our data demonstrate that the presenilin mutations cause a dominant gain of function and may induce AD by enhancing A beta 42 production, thus promoting cerebral beta-amyloidosis.
Alzheimer Disease↗
Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia in first remission.
The purpose of the study was to evaluate the feasibility and efficacy of high-dose cytarabine-anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for adult patients with acute myelogenous leukemia in first remission. Fifty-nine consecutive patients (median age 45, range 18-69) with acute myelogenous leukemia in first remission were enrolled on a study of high-dose cytarabine-mitoxantrone consolidation chemotherapy used as a method of in vivo purging for the purpose of autologous peripheral blood progenitor cell transplantation. A median of 7 x 10(8) peripheral blood mononuclear cells/kg were infused 1 day after preparative conditioning with 11.25 Gy total body irradiation and cyclophosphamide (120 mg/kg). Forty-six patients received myeloablative chemo-radiotherapy followed by the infusion of chemotherapy/rHu-G-CSF-mobilized autologous peripheral blood progenitor cells. The median time to both neutrophil and platelet recovery from transplant was 15 days (range, 11-36 and 5-253+ days, respectively). After a median follow-up of 27 months, 31 patients remain alive with 27 in complete remission. Median remission duration for all eligible patients is 12 months, and actuarial leukemia-free survival at 3 years is 42 +/- 14%. The actuarial risk of relapse is 54 +/- 15%. Toxicity of autologous peripheral blood progenitor cell transplant included treatment-related death in two patients and grade III/IV organ toxicity in six. Advanced age was a negative prognostic factor for leukemia-free survival. Our results demonstrate that autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible in an unselected population of adult patients with acute myelogenous leukemia in first remission producing improved leukemia-free survival with minimal toxicity.
Adult↗
Intracellular colocalisation of the translationally controlled protein P23 with cytoskeletal structures.
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3T3 Cells↗
Development and validation of a geriatrics knowledge test for primary care residents.
This study reports the development and preliminary validation of an instrument to measure geriatrics knowledge of primary care residents. A 23-item test was developed using questions selected from the American Geriatrics Society's Geriatrics Review Syllabus. Ninety-six internal medicine and family practice residents, 14 geriatrics fellows, and 11 geriatrics faculty members participated in the study. Findings support the reliability (Cronbach's alpha = 0.66) and validity (content and "known groups") of this short test. Predictive validity and sensitivity of the test to changes in knowledge will have to be further explored as residents progress through their training.
Adult↗
Nasal mucosal cell alterations in HIV-infected patients.
Patients with HIV infection often have nasopharyngeal symptoms related to inflammatory or infectious diseases of the upper respiratory tract. In this study, we examined specific nasal mucosal cytologic alterations in adult patients with HIV infection for associations with nasopharyngeal symptoms and other clinical parameters. Mucosal cytology was obtained in 62 patients from an urban HIV clinic using a plastic curettelike probe. The quantities of goblet cells, vacuolated cells, and leukocytes were determined and analyzed for associations with various clinical aspects of these patients and specifically with the presence or absence of prolonged (> 2-week duration) nasopharyngeal symptoms. Goblet cell, but not vacuolated cell, increases were observed in samples in which nasal eosinophilia was present and in samples obtained from April to October without specific associations with nasopharyngeal symptoms or histories of atopic disease. A history of allergic rhinitis or recent upper respiratory infection was significantly associated with increased proportions and total numbers of epithelial cells that showed vacuolization. In patients with prolonged nasopharyngeal symptoms, significantly higher numbers of nasal leukocytes were observed but higher proportions of vacuolated cells were not. Scores of tests for abnormal physical findings in the nose were higher for patients with prolonged nasopharyngeal symptoms than for those without. Peripheral blood CD4 concentrations, gender, nasal substance abuse history, and other comorbidities did not influence either vacuolated cell or goblet cell quantities. These data show that prolonged nasopharyngeal symptoms in HIV infection are associated with a certain nasal cellular pattern. It is conceivable that this pattern relates to recurrent or prolonged nasal inflammation secondary to upper respiratory infection.
Adult↗
Naturally occurring muscle pain during exercise: assessment and experimental evidence.
The objectives were: (i) to present a method for assessing muscle pain during exercise, (ii) to provide reliability and validity data in support of the measurement tool, (iii) to test whether leg muscle pain threshold during exercise was related to a commonly used measure of pain threshold pain during test, (iv) to examine the relationship between pain and exertion ratings, (v) to test whether leg muscle pain is related to performance, and (vi) to test whether a large dose of aspirin would delay leg muscle pain threshold and/or reduce pain ratings during exercise. In study 1, seven females and seven males completed three 1-min cycling bouts at three different randomly ordered power outputs. Pain was assessed using a 10-point pain scale. High intraclass correlations (R from 0.88 to 0.98) indicated that pain intensity could be rated reliably using the scale. In study 2, 11 college-aged males (age 21.3 +/- 1.3 yr) performed a ramped (24 W.min-1) maximal cycle ergometry test. A button was depressed when leg muscle pain threshold was reached. Pain threshold occurred near 50% of maximal capacity: 50.3 (+/- 12.9% Wmax), 48.6 (+/- 14.8% VO2max), and 55.8 (+/- 12.9% RPEmax). Pain intensity ratings obtained following pain threshold were positively accelerating function of the relative exercise intensity. Volitional exhaustion was associated with pain ratings of 8.2 (+/- 2.5), a value most closely associated with the verbal anchor "very strong pain." In study 3, participants completed the same maximal exercise test as in study 2 as well as leg cycling at 60 rpm for 8 s at four randomly ordered power outputs (100, 150, 200, and 250 W) on a separate day. Pain and RPE ratings were significantly lower during the 8-s bouts compared to those obtained at the same power outputs during the maximal cycle test. The results suggest that noxious metabolites of muscle contraction play a role in leg muscle pain during exercise. In study 4, moderately active male subjects (N = 19) completed two ramped maximal cycle ergometry tests. Subjects drank a water and Kool-Aid mixture, that either was or was not (placebo) combined with a 20 mg.kg-1 dose of powdered aspirin 60 min before exercise. Paired t-tests revealed no differences between conditions for the measures of exercise intensity at pain threshold [aspirin vs placebo mean (+/- SD)]: power output: 150 (+/- 60.3 W) versus 153.5 (+/- 64.8 W); VO2: 21.3 (+/- 8.6 mL.kg-1.min-1) versus 22.1 (+/- 10.0 mL.kg-1.min-1); and RPE: 10.9 (+/- 3.1) versus 11.4 (+/- 2.9). Repeated measures ANOVA revealed no significant condition main effect or condition by trial interaction for pain responses during recovery or during exercise at 60, 70, 80, 90, and 100% of each condition's peak power output. It is concluded that the perception of leg muscle pain intensity during cycle ergometry: (i) is reliably and validly measured using the developed 10-point pain scale, (ii) covaries as a function of objective exercise stimuli such as power output, (iii) is distinct from RPE, (iv) is unrelated to performance of the type employed here, and (v) is not altered by the ingestion of 20 mg.kg-1 acetylsalicylic acid 1 h prior to the exercise bout.
Adolescent↗
Autonomic differences between athletes and nonathletes: spectral analysis approach.
The purpose of this study was to assess the adaptive effects of endurance training on autonomic function in athletes with spectral analysis of cardiovascular variability signals. Continuous ECG, arterial blood pressure (ABP), and respiratory signals were recorded from 15 athletes (VO2max > 55 mL.min-1.kg-1) and 15 nonathletes (VO2max < 45 mL.min-1.kg-1) during 10 min at sitting position. Autonomic function was assessed by low frequency power (LF power: 0.06-0.14 Hz) and high frequency power (HF power: the region of the respiratory frequency based on respiratory spectrum) obtained from the autospectra of RR interval, systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) variability signals. The spontaneous baroreflex sensitivity was evaluated by the moduli, BRSLF and BRSHF, of the transfer function between RR interval and SAP variability in LF and HF bands. The resting HR in athletes was significantly lower than that in nonathletes. The HF power, an index of parasympathetic activity, in RR interval spectra were significantly higher in athletes than in nonathletes. Meanwhile, the LF power (an indicator of sympathetic activities contributing to RR interval and of ABP variabilities) showed no significant difference between both groups, although that of athletes was slightly less than that of nonathletes. Also, BRSLF and BRSHF were not significantly different between athletes and nonathletes. These results indicate that endurance training results in the enhanced vagal activities in athletes, which may contribute in part to the resting bradycardia.
Adult↗
Transverse carpal ligament: its effect on flexor tendon excursion, morphologic changes of the carpal canal, and on pinch and grip strengths after open carpal tunnel release.
A three-part study is described that examines postoperative weakness after open carpal tunnel release and investigates the role of the transverse carpal ligament in the digital flexor pulley system. The effect of this ligament on flexor tendon excursion is evaluated in a cadaver study. Magnetic resonance imaging analysis is used to determine whether division of the transverse carpal ligament promotes volar migration of the median nerve and flexor tendons. Finally, the effects of ligament division and various methods of transverse carpal ligament reconstruction on the return of grip and pinch strengths after open carpal tunnel release are evaluated. The authors were able to determine that transverse carpal ligament reconstruction, particularly the transposition flap repair technique, after open carpal tunnel release confers a mechanical advantage and that the transverse carpal ligament is an important pulley for flexor tendon excursion. Based on the magnetic resonance imaging studies, volar displacement of carpal contents is reduced in patients undergoing transverse carpal ligament reconstruction by means of a transposition flap compared with those undergoing no ligament reconstruction and those undergoing reconstruction using the palmar aponeurosis. Postoperative grip and pinch strength values for the transposition flap repair group surpassed those of the other two groups at 12 weeks.
Carpal Tunnel Syndrome↗
A severely defective TATA-binding protein-TFIIB interaction does not preclude transcriptional activation in vivo.
In yeast cells, mutations in the TATA-binding protein (TBP) that disrupt the interaction with the TATA element or with TFIIA can selectively impair the response to acidic activator proteins. We analyzed the transcriptional properties of TBP derivatives in which residues that directly interact with TFIIB were replaced by alanines. Surprisingly, a derivative with a 50-fold defect in TBP-TFIIB-TATA complex formation in vitro (E188A) supports viability and responds efficiently to activators in vivo. The E186A derivative, which displays a 100-fold defect in TBP-TFIIB-TATA complex formation, does not support viability, yet it does respond to activators. Conversely, the L189A mutation, which has the mildest effect on the interaction with TFIIB (10-fold), can abolish transcriptional activation and cell viability when combined with mutations on the DNA-binding surface. This "synthetic lethal" effect is not observed with E188A, suggesting that the previously described role of L189 in transcriptional activation may be related to its location on the DNA-binding surface and not to its interaction with TFIIB. Finally, when using TBP mutants defective on multiple interaction surfaces, we observed synthetic lethal effects between mutations on the TFIIA and TFIIB interfaces but found that mutations implicated in association with polymerase II and TFIIF did not have significant effects in vivo. Taken together, these results argue that, unlike the TBP-TATA and TBP-TFIIA interactions, the TBP-TFIIB interaction is not generally limiting for transcriptional activation in vivo.
Alanine↗