Detection of recombinant and endogenous mouse melatonin receptors by monoclonal antibodies targeting the C‐terminal domain

Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT₁ and MT₂, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT₁ and MT₂. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT₁ and MT₂ by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT₁ or MT₂. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT₂ expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies.     

QT prolongation under sevoflurane in infants

Introduction   QT interval prolongation may cause the potentially lethal tachyarrhythmia torsades de pointes ( 1 ). The cause of the QT interval prolongation may be a congenital mutation in genes encoding cardiac potassium and sodium channels ( 2 ) or be acquired following drug administration ( 3 ) or metabolic disorders ( 4 ). Among a few other drugs volatile anaesthetics prolong the QT interval. During the last few years sevoflurane has become the most used volatile anaesthetic for the induction of anaesthesia in infants.
Methods   This investigation, on infants aged from 1 to 6 months, was approved by the institutional ethic committee. Thirty-six otherwise healthy infants due to elective surgery were included in our study The patients were randomly assigned to one of two treatment groups. Group S ( n  = 24) was anaesthetised with sevoflurane, Group H was anaesthetised with halothane. ECG recordings were taken before the anaesthesia onset, 15 min after the first contact with the volatile anaesthetic and 60 min after the ending of the volatile gas exposition. QTc interval was calculated using the Bazett's formula ( 5 ).
Results   QTc interval was significantly ( P < 0.0002) (Table 1) lengthened 15 min after anaesthesia induction with sevoflurane as well as 60 min ( P < 0.01) after the ending of the gas exposition without any difference in age and gender. The QTc interval in patients anaesthetised with halothane did not show any significant change.  

  Table 1     

3.

Mechanism of bronchodilator effect in chronic airflow limitation.   总被引：1，自引：0，他引：1       下载免费PDF全文

R Jaeschke  G H Guyatt  J Singer  J Keller    M T Newhouse 《Canadian Medical Association journal》1991,144(1):35-39

OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities. METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined. RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001). CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance.     

4.

Finite two-dimensional phospholipid crystals          下载免费PDF全文

H. M. McConnell  D. J. Keller 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(14):4706-4708

     

5.

Benign symmetrical lipomatosis     

S M Keller  J S Waxman  U S Kim 《Southern medical journal》1986,79(11):1428-1429

Benign symmetrical lipomatosis is an unusual disorder of fat metabolism that results in a characteristic accumulation of adipose tissue around the head and neck. Surgical extirpation is the only known effective therapy. Physical examination does not provide a comprehensive delineation of tumor extent. We present the first reported use of CT scanning to investigate the anatomic limits of BSL and to plan the operative approach.     

6.

T cell subsets in human colostrum     

M A Keller  J Faust  L J Rolewic  D D Stewart 《Journal of pediatric gastroenterology and nutrition》1986,5(3):439-443

Lymphocytes from 10 paired colostrum and peripheral blood specimens were examined to determine if the colostral T cell population differs from the peripheral blood T cell population in subset distribution. The percentages of lymphocytes staining with OKT3, OKT4, and OKT8 murine monoclonal antibody were determined. Lymphocytes from colostrum were 74.7 +/- 2.5% OKT3+, 50.6 +/- 2.3% OKT4+, 24.0 +/- 1.7% OKT8+, whereas peripheral blood lymphocytes were 78.7 +/- 1.9% OKT3+, 48.4 +/- 1.4% OKT4+, and 29.8 +/- 1.6% OKT8+. The percentage of colostrum lymphocytes positive for OKT3 was significantly although not strikingly lower than the OKT3 percentage for blood lymphocytes (p less than 0.05). This difference was due to the lower percentage of OKT8 positive lymphocytes in colostrum compared with blood (p less than 0.01). Although the T cell subset distribution of colostrum generally appears to be similar to that in the peripheral blood, there were small differences in OKT3 and OKT8 percentages that were statistically significant suggesting the possibility of some selectivity of the colostral T cell population.     

7.

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.     

Heiko Sch?der  Diane L Carlson  Dennis H Kraus  Hilda E Stambuk  Mithat G?nen  Yusuf E Erdi  Henry W D Yeung  Andrew G Huvos  Jatin P Shah  Steven M Larson  Richard J Wong 《Journal of nuclear medicine》2006,47(5):755-762

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

8.

Sexual and Drug Use Risk Behaviors of Long-Haul Truck Drivers and Their Commercial Sex Contacts in New Mexico     

Donna Hubbard McCree  Shannon Cosgrove  Dale Stratford  Sarah Valway  Nick Keller  Jaime Vega-Hernandez  Steven A. Jenison 《Public health reports (Washington, D.C. : 1974)》2010,125(1):52-60

     

9.

What is the value of minimizing access trauma for patients?]     

P Hildebrand  U J Roblick  R Keller  M Kleemann  L Mirow  H-P Bruch 《Der Chirurg》2007,78(6):494, 496-494, 500

Minimizing the access trauma of surgical interventions is becoming an essential task in modern surgery in order to make the treatment more comfortable for the patient. Minimally invasive surgery has had a major impact on the improvement of surgical results over the last decade. This is why such surgery is often named as the third patient friendly revolution in surgery after the introduction of asepsis and anesthesia. Operations that caused a huge strain on the patients in the past and led to immense costs for society because of the patient's lost working time and extensive rehabilitation, have lost their fear thanks to this technique. The physical strain is lower, the cosmetic effect is considerable and the costs for society might be reduced due to the significantly shorter duration of convalescence.Despite its known advantages, which have been reported in numerous studies, minimally invasive surgery has recently gained increased interest because of the installation of new accounting systems as well as strict budgeting and restricted resources.Realistic cost-benefit analysis and objectified quality controls are needed in order to guarantee innovative and patient friendly basic approaches in medicine in the future.     

10.

Evaluation and Imaging of the Patellofemoral Joint     

Julie M. Keller MD  William N. Levine MD   《Operative Techniques in Orthopaedics》2007,17(4):204-210

     

1 [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] 下一页 » 末  页»

Mechanism of bronchodilator effect in chronic airflow limitation.

OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities. METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined. RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001). CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance.     

Benign symmetrical lipomatosis

Benign symmetrical lipomatosis is an unusual disorder of fat metabolism that results in a characteristic accumulation of adipose tissue around the head and neck. Surgical extirpation is the only known effective therapy. Physical examination does not provide a comprehensive delineation of tumor extent. We present the first reported use of CT scanning to investigate the anatomic limits of BSL and to plan the operative approach.     

T cell subsets in human colostrum

Lymphocytes from 10 paired colostrum and peripheral blood specimens were examined to determine if the colostral T cell population differs from the peripheral blood T cell population in subset distribution. The percentages of lymphocytes staining with OKT3, OKT4, and OKT8 murine monoclonal antibody were determined. Lymphocytes from colostrum were 74.7 +/- 2.5% OKT3+, 50.6 +/- 2.3% OKT4+, 24.0 +/- 1.7% OKT8+, whereas peripheral blood lymphocytes were 78.7 +/- 1.9% OKT3+, 48.4 +/- 1.4% OKT4+, and 29.8 +/- 1.6% OKT8+. The percentage of colostrum lymphocytes positive for OKT3 was significantly although not strikingly lower than the OKT3 percentage for blood lymphocytes (p less than 0.05). This difference was due to the lower percentage of OKT8 positive lymphocytes in colostrum compared with blood (p less than 0.01). Although the T cell subset distribution of colostrum generally appears to be similar to that in the peripheral blood, there were small differences in OKT3 and OKT8 percentages that were statistically significant suggesting the possibility of some selectivity of the colostral T cell population.     

18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

What is the value of minimizing access trauma for patients?]

Minimizing the access trauma of surgical interventions is becoming an essential task in modern surgery in order to make the treatment more comfortable for the patient. Minimally invasive surgery has had a major impact on the improvement of surgical results over the last decade. This is why such surgery is often named as the third patient friendly revolution in surgery after the introduction of asepsis and anesthesia. Operations that caused a huge strain on the patients in the past and led to immense costs for society because of the patient's lost working time and extensive rehabilitation, have lost their fear thanks to this technique. The physical strain is lower, the cosmetic effect is considerable and the costs for society might be reduced due to the significantly shorter duration of convalescence.Despite its known advantages, which have been reported in numerous studies, minimally invasive surgery has recently gained increased interest because of the installation of new accounting systems as well as strict budgeting and restricted resources.Realistic cost-benefit analysis and objectified quality controls are needed in order to guarantee innovative and patient friendly basic approaches in medicine in the future.