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.     

Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery

BACKGROUND: Abnormalities in calcium and vitamin D metabolism have been reported after bariatric surgery. The purpose of this study was to evaluate vitamin D nutritional status among morbidly obese patients before gastric bypass surgery. METHODS: We prospectively studied 279 morbidly obese patients seeking gastric bypass surgery for vitamin D nutritional status as assessed by serum 25-hydroxyvitamin D level. In addition, serum samples were analyzed for calcium, alkaline phosphatase (AP), intact parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D. RESULTS: Mean patient age was 43 +/- 9 years; 87% of the study patients were women, and 72% were white. Serum calcium and AP levels were normal in 88% and 89% of the patients, respectively. Vitamin D depletion, defined as serum 25-hydroxyvitamin D level 相似文献   

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     

6.

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.     

7.

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

     

8.

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.     

9.

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.     

10.

Pulmonary Thromboendarterectomy     

Steven R. Meyer MD  PhD  Christopher G.A. McGregor MB  FRCS  MD 《Operative Techniques in Thoracic and Cardiovascular Surgery》2007,11(4):785-263

     

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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.