Peptide hormones and their possible functions in the normal and abnormal lung.
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Biomedical subjects
Publications and source records attributed to K L Becker.
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Performance appraisal can be an emotionally charged experience for both the supervisor and the employee. The accuracy of the appraisal is dependent not only upon the evaluator, but also upon the appropriateness of the tool being used for the task. An employee's career advancement, professional development, monetary remuneration and self-esteem often may depend upon the final outcome of the process. A group of nurse practitioners practicing in a wide variety of clinical and administrative roles at the Johns Hopkins Hospital formed a task force to develop a performance appraisal tool that would adequately reflect the nurse practitioner role and that could be individualized according to the work setting. A general overview of the development process, the tool, its scoring system and instructions for implementation are presented.
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Immunoreactive calcitonin (iCT) has been localized in solitary endocrine cells and in clusters of these cells, called neuroepithelial bodies, in human and hamster lungs. It has been demonstrated that hyperplasia of hamster lung endocrine cells occurs following exposure to diethylnitrosamine (DEN), a systemic carcinogen. In the present study we have investigated iCT as a hormonal correlate of DEN-induced pulmonary endocrine cell hyperplasia in hamsters. Hamsters were given 3 mg of DEN per animal, subcutaneously, twice a week and then serially sacrificed at 2, 4, 8, and 12 weeks. By immunocytochemistry, iCT-containing cells could be demonstrated in thyroids, tracheal glands, and throughout the airway epithelium. At 8 or 12 weeks of DEN exposure, one to eight neuroepithelial bodies with iCT-containing cells were identified per square centimeter of lung sections, in contrast to zero to one neuroepithelial bodies/cm2 in control hamsters. By radioimmunoassay, pulmonary iCT increased significantly at 8 weeks of DEN exposure, amounting to 3.5-fold the control values at 12 weeks. Serum iCT increased at 4 weeks of exposure and by 12 weeks had tripled (183 +/- 62 pg/ml, mean +/- SD, p less than 0.001), as compared with control animals. Subsequently, DEN was stopped for 4 weeks, and the levels of both serum and lung iCT decreased, although they remained higher than those of controls. The serum and lung iCT of control hamsters was constant throughout the experiment (49 +/- 26 pg/ml and 1754 +/- 489 pg/gm of wet weight, mean +/- SD, respectively). Thyroidal iCT levels of exposed hamsters did not differ from those of the controls; both increased progressively. The DEN-exposed animals had retarded growth as compared with the controls. Column chromatography using superfine Sephadex G-75 demonstrated that both DEN-exposed and control lungs contained iCT with a predominant molecular size corresponding to the dimer of synthetic human calcitonin; whereas thyroidal iCT was mostly monomeric (approximately 3,500 daltons). The increase of pulmonary iCT correlates well with the 4-fold increase of pulmonary endocrine cells, reported earlier following similar DEN exposure. We conclude that iCT levels of hamster sera and lungs can be used as a biochemical parameter to monitor hyperplasia of the pulmonary endocrine cells in these animals.
A study was made of immunoreactive calcitonin (iCT) secretion by continuous cultures of small cell carcinoma of the lung (SCCL). Using an antiserum region specific for the midportion of the molecule, 9/12 cultures were found to secrete iCT. Gel filtration studies were performed on both supernatant fluid (SF) and cell pellet (CP) extract from a culture secreting high levels of iCT. Multiple iCT fractions were found in the SF with the major fraction being of high molecular weight (MW). In contrast, the CP had apparently monomeric CT as its principal iCT fraction. These studies demonstrate frequent iCT secretion by SCCL cultures and significant disparities between the iCT moieties found extra- and intracellularly.
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The metabolic effects of acebutolol, a cardioselective beta-adrenergic blocker, and of propranolol, a nonselective beta blocker, were evaluated. Our subjects were 20 men with chronic stable angina; none had diabetes. An initial 4-wk, single-blind control phase was followed by two drug treatment periods, each a 3-wk double-blind titration phase (using increasing doses of acebutolol or propranolol), followed by a 5-wk double-blind maintenance phase. Metabolic studies were performed at the end of the control and maintenance phases. Propranolol induced elevation in basal serum glucose concentrations and both propranolol and acebutolol decreased glucose tolerance at 2.5 and 3 hr. There was no noticeable effect on insulin secretion by either drug. Neither propranolol nor acebutolol induced hyperlipidemia. There was a small decrease in total serum cholesterol after propranolol. Both drugs decreased low-density lipoprotein cholesterol. No effects were noted on the levels of serum triglycerides, high-density lipoprotein cholesterol, or free fatty acids.
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The bronchial Kulchitsky cells are scattered specific cells which lie close to the basement membrane of the bronchi and bronchioles. Electron microscopy reveals that they contain electron-dense granules similar to that seen in cells with a known endocrine function. In addition, experimentally induced degranulation of the K cell suggestive of a secretory process, and the likelihood that these cells are precursors of small cell lung carcinoma (which often elaborates humoral substances) has led to the postulate that this bronchial cell serves a humoral role of either a paracrine or endocrine nature. We have found that the bronchial K cell of man contains a calcitonin-like polypeptide which, immunologically and chemically, is not dissimilar to the hormone produced by the C cells of human thyroid. This finding may help explain the persistence of serum immunoreactive calcitonin (iCT) after total thyroidectomy, the fact that thyroidectomized man does not manifest any profound alteration of calcium metabolism, and why small cell cancer of the lung is frequently associated with hypercalcitonemia. In addition, the finding of K cell hyperplasia in chronic bronchitis and emphysema may explain the occurrence of hypercalcitonemia in patients with these diseases and some lung cancers of cell types other than the small cell variety. Further studies are needed to elucidate the role of K cell iCT, and to determine what other hormones might also be elaborated by this diffuse system of bronchial cells.
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Serum and urinary calcitonin levels were measured in patients with acute and chronic inflammatory diseases of the lung. Using both carboxyl terminal and midportion antisera, the incidence of increased immunoreactive values of this hormone was 68 percent for patients with emphysema, 59 percent for tuberculosis, and 89 percent for acute bacterial pneumonitis. In order to determine the source of the high levels of calcitonin, immunoperoxidase stains were made of sections of human lung; the hormone was found within the bronchial Kultschitzky cell (K cell). This suggests a specific endocrine role for the K cell, and may explain not only the high calcitonin levels in patients with inflammatory lung disease, but also the high levels associated with both carcinoid tumor and small cell carcinoma, which may originate from K cells. It is apparent that moderately high levels of calcitonin in a patient with pulmonary disease cannot always be associated with tumor.
Calcitonin, the hypocalcemic, hypophosphatemic polypeptide hormone of C cell origin, has been reported to be high in pregnant women at delivery. Levels of this hormone were determined by radioimmunoassay in 56 pregnant women in all trimesters and found to be above normal in 72 percent. Values were also increased during the first two days postpartum. Calcitonin levels were not correlated with serum calcium or phosphate, except in the first trimester when levels of this hormone were inversely correlated with serum phosphate. Perhaps the hypercalcitonemia of pregnancy serves to protect the maternal skeleton, while allowing the fetus to accumulate calcium.
Gastrin has been suggested as a natural secretogogue of the hormone calcitonin. We have found hypercalcitonemia in 55% of patients with pernicious anemia, and the gastrin levels, although usually increased, did not correlate.
We have detected immunoreactive calcitonin (iCT) in the cerebrospinal fluid (CSF) of normal individuals. Using an antibody with midportion recognition, the mean +/- S.D. of the cerebrospinal iCT in 27 normal subjects was 28 +/- 14 pg/ml. The mean serum iCT was 89 +/- 68 pg/ml, the CSF/serum distribution ratio being 0.31. There were no significant correlations between CSF iCT or serum iCT and the calcium, magnesium, phosphate, sodium, potassium or chloride in the CSF or serum. Although there was a trend for serum iCT values to be related to CSF iCT values, it did not attain statistical significance. The demonstration that the CSF contains iCT may have important physiologic implications, and its measurement offers a useful parameter to study its effects on calcium metabolism and/or other aspects of brain function.
Immunochemical studies indicate that immunoreactive calcitonin (iCT) is present in many tissues of monkey following thyroidectomy (thx) (e.g. liver, thymus, lung). Extrathyroidal iCT may play a role in calcium metabolism.
We demonstrated previously that high serum calcitonin values in bronchogenic carcinoma are useful clinically as a parameter of progress of the disease and response to therapy. After developing a procedure for the measurement of calcitonin in urine, we studied serum and urine levels in 41 patients with lung cancer, using both a carboxyl terminus and a midportion recognizing antiserum. In general, midportion antiserum was more useful. Urine calcitonin measurements alone were superior to serum in terms of numbers of patients having increased values with one or both antisera (76% vs 46%). When both antisera were used to assay both serum and urine, 90% of patients had abnormal values. Once a tissue diagnosis has been established, the radioimmunoassay of urinary calcitonin offers a new dimension to the utility of this hormone as a marker for bronchogenic carcinoma.
Because of the persistence of serum and/or urinary calcitonin in patients with thyroidectomies and the presence of high levels of immunoreactive calcitonin in the pulmonary tissue of primates with intact thyroids and primates on whom thyroidectomies were done, an immunocytochemical study was made of the lungs of human neonates. With the use of a specific antibody to calcitonin and the application of immunoperoxidase staining, reactivity was located within the bronchial and bronchiolar Kulchitsky (K) cells. This study, which strongly suggests that these cells have an endocrine role, offers a pathophysiologic rationale for the high calcitonin levels associated with the carcinoid tumor and small cell carcinoma, which may originate from the K cell. In addition, this study may explain why the removal of the thyroid gland is not followed by a profound change in calcium metabolism.