PubMed Health⌕ Search

Biomedical subjects

R H Snider

Publications and source records attributed to R H Snider.

At least 37 records · Page 2Linked to original sources
PubMed1995

Late pulmonary sequela following burns: persistence of hyperprocalcitonemia using a 1-57 amino acid N-terminal flanking peptide assay.

Seven patients were evaluated at a mean duration of 8.4 yr after sustaining inhalational injury associated with burns. At the time of re-examination, the patients were asymptomatic and had normal chest X-rays, and arterial blood gases. Three of the seven patients had abnormally elevated serum calcitonin levels. The spirometry (FEV1) measurements showed an inverse trend to that of the serum calcitonin levels. The elevated calcitonin levels had an abnormal predominance of the procalcitonin component as assessed by several region specific antisera. The serum calcitonin also showed a significant correlation with the hormone level which had been obtained at the time of prior discharge from the hospital (r = 0.91). Although there appears to be no or minimal chronic pulmonary sequela to inhalational injury in burns by pulmonary testing, we speculate that the hyperprocalcitonemia in some of the patients may reflect a long-term hyperplastic response of the bronchio-epithelial pulmonary neuroendocrine cells. The potential significance of this and other lung-associated endocrine markers is discussed.

Biomarkers↗
PubMed1994

Small cell lung carcinoma cell lines express mRNA for calcitonin and alpha- and beta-calcitonin gene related peptides.

Calcitonin (CT) and calcitonin gene related peptide (CGRP) are derived from preprohormones encoded by three mRNAs (CT, alpha-CGRP and beta-CGRP) from two genes (CALC1 and CALC2) on chromosome 11. Among 16 small cell lung cancer cell lines examined by RNase protection assay, 9 (56%) had detectable CT mRNA, 8 (50%) had alpha-CGRP mRNA, and 13 (81%) had beta-CGRP mRNA. At least one CALC1 transcript (CT or alpha-CGRP) was found in 11 (69%) cell lines with three having only CT mRNA, two having only alpha-CGRP mRNA, and six having both. beta-CGRP mRNA was detected in all of these 11 cell lines expressing a CALC1 transcript. Immunoreactive CT was detected by radioimmunoassay in eight of nine SCLC cell lines expressing CT mRNA, and immunoreactive CGRP was detected in 12 of 13 cell lines expressing a CGRP mRNA. The variety of expression of these three peptides in different cell lines of the same cell type should provide a useful system for further study of the control of expression of these peptides.

Calcitonin↗
PubMed1994

Calcitonin elevation in small cell lung cancer without ectopic production.

To determine the relative contribution of ectopic calcitonin (CT) production versus nonectopic secretion of CT in patients with small cell lung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 86 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previously untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermediate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for determination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iCT in eight of 16. The tumor cell lines of seven patients had undetectable CT by both RPA and RIA, and of these, five had elevated urine or serum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA and iCT by RIA, but in none of six whose tumor cell lines had undetectable CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.

Adult↗
PubMed1993

Cholinergic-nicotinic control of growth and secretion of cultured pulmonary neuroendocrine cells.

Dispersed newborn hamster lung cells were established in vitro in a defined, low-serum growth medium. Neuroendocrine markers (immunohistochemistry for bombesin/gastrin-releasing peptide and calcitonin) revealed a cellular predominance of pulmonary neuroendocrine (PNE) cells. While the supernatant concentration remained stable, the concentration of PNE cell immunoreactive calcitonin (iCT) gradually declined over 4 weeks. Supplementation of the medium with nicotine for 3 weeks prevented this decline in cellular iCT. Concurrently, the number of cells and [3H]thymidine incorporation were significantly increased. The stimulatory effect of chronic nicotine was reversed by the coadministration of the nicotinic antagonist hexamethonium. In another set of experiments, prior multiple transplacental nicotine pretreatments resulted in a significant increase in iCT in the lungs of newborns; when these lungs were subsequently placed in cell culture without nicotine, despite the higher concentration of iCT, there was a drop in iCT similar to that observed in the control culture. In contrast, in vivo, the lung iCT remained significantly elevated at 1 week post-parturition. Cell culture supernatants were analyzed at week 4 for the evoked release of iCT; cholinergic-nicotinic agonists promptly increased the supernatant iCT, which was blocked by nicotinic but not by muscarinic antagonists. We suggest that this in vitro system provides a useful tool to study directly the PNE cell. The acute and chronic effects of nicotine are most likely related to stimulation of cholinergic-nicotinic receptors on iCT-containing PNE cells.

Animals↗
PubMed1993

Heterogeneity studies of hamster calcitonin following acute exposure to cigarette smoke: evidence for monomeric secretion.

Various acute stimuli, including cigarette smoke, induce hypercalcitonemia in man and hamsters. We have shown that this occurs also in thyroidectomized subjects. In the present study we have further explored this phenomenon of secretion from the lungs by studying, simultaneously, the HPLC characteristics of pulmonary tissue and serum in control hamsters and in animals immediately following short-term exposure to cigarette smoke. In addition, we have studied the immunoheterogeneity of lung calcitonin 24 hours following the acute exposure. Control lungs contained monomeric immunoreactive calcitonin (M-iCT), high molecular mass iCT (H-iCT), and CT fragments. Immediately following smoke exposure, there was an acute decrease of lung iCT by radioimmunoassay (RIA) which consisted primarily of a decrease in M-iCT by HPLC. Simultaneously, the iCT increase in the serum by RIA was shown by HPLC to involve M-iCT. Twenty-four hours after smoke inhalation, the lung iCT by RIA and M-iCT by HPLC had returned towards control levels. These findings document the molecular characteristics of lung iCT following acute cigarette smoke stimulation, and suggest that under certain circumstances M-iCT may be actively secreted by the lung. It remains to be determined whether this type of secretion reflects hemocrine or paracrine release and what the physiological role for such a secretion may be.

Animals↗
PubMed1992

Serum procalcitonin as an index of inhalation injury in burns.

The molecular heterogeneity of serum immunoreactive calcitonin (iCT) was analyzed from a prospective study of 41 burn patients. Using different region-specific anticalcitonin antisera, the ratio of mid-region-recognizing to carboxyl terminal-region-recognizing iCT was found to increase acutely in those who subsequently died. The highest ratios occurred in those who died early of respiratory complications. Sephadex chromatography and reversed-phase HPLC demonstrated that the serum iCT circulated predominantly in the large molecular mass prohormone form (16 kDa). In comparison, iCT of normal human lung and of normal thyroid was shown to consist primarily of smaller monomeric mass forms. Furthermore, in 12 normal volunteers who were evaluated with a calcium-pentagastrin infusion, the ratio of iCT levels did not differ from the baseline ratio despite a 50% increase in serum iCT. These results suggest that in burns, the inhalational injury-associated hypercalcitonemia is characterized by a preferential release of procalcitonin; a form of constitutive secretion. The measurement of serum procalcitonin levels would appear to be a useful prognostic indicator of the severity of inhalational injury occurring in burn patients.

Biomarkers↗
PubMed1990

Modulation of pulmonary bombesin by nicotine and vagotomy.

In pregnant hamsters, three transplacental injections of the ganglionic agonist nicotine resulted in a dose-dependent decrease in the concentration of mammalian bombesin (MB) in the lungs of neonatal (1 day old) animals. This decrease in neonatal MB did not occur if nicotine was given only once during gestation, or when it was given three times in conjunction with the ganglionic antagonist mecamylamine. In one week old animals born of mothers who had been exposed to three doses of nicotine during gestation, lung MB had returned to control levels. When nicotine was injected into neonatal animals, lung MB acutely increased. Right sided vagotomy to young hamsters resulted in an increase in the ratio of lung MB (right vs. left lobe) 1 week after surgery. Administration of nicotine to vagotomized animals resulted in decreased total lung MB and normalization of the MB ratio. Thus, nicotine has a potent modulatory influence on lung MB during fetal and neonatal development and maturation. This influence is also present in young animals that are subjected to partial denervation. Our hypothesis is that the innervation of pulmonary neuroendocrine (PNE) cells influences both PNE cell growth and its synthetic function. PNE MB, which is an epithelial and neoplastic growth factor, may play a role in this response.

Animals↗
PubMed1990

Pulmonary bombesin and calcitonin in hamsters during exposure to hyperoxia and diethylnitrosamine.

Combined exposure of hamsters to 60% hyperoxia and the carcinogen diethylnitrosamine for 6 wk resulted in the development of lung tumors. This was associated with progressive loss of body weight as well as increases in the pulmonary-associated peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT). After 3 wk of exposure, multiple bronchial epithelial hyperplastic foci were noted, along with increased lung levels of MB and iCT as well as increased serum levels of MB. At this time, immunocytochemistry revealed the presence of MB and iCT within hyperplastic pulmonary neuroendocrine (PNE) cells. In addition, the localization of MB to alveolar type II cells was noted, along with the presence of lamellar bodies and secretion granules in these cells on electron microscopy. After 6 wk of exposure, distinctive microscopic pulmonary tumorlets were seen. These tumorlets were associated with a marked increase in lung and serum MB, and to a lesser extent lung and serum iCT. At this time, MB and iCT were localized exclusively to these abnormal PNE cell sites. These results, which may have relevance in humans, suggest that endogenous peptides may be important components in the process of development of neuroendocrine cancer.

Animals↗
PubMed1989

Stimulation of hamster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke.

Although the normal function of pulmonary neuroendocrine (PNE) cells containing bioactive peptides is poorly understood, various pulmonary diseases are associated with hyperplasia of these cells, and they also may be progenitors for small cell lung cancer in humans. In this study we have investigated the effects of subchronic cigarette smoke exposure in the hamster on the PNE cells and their peptide content. Daily exposure to standard research cigarette smoke for as long as 90 days led to progressively higher levels of serum calcitonin (iCT) as well as higher lung tissue iCT and the gastrin releasing-like peptides or mammalian bombesin (MB). Subsequent to a 30-day period during which there was no further exposure to smoke, serum levels returned to control levels, but the lung levels of both iCT and MB remained higher than control levels. Also, after the 90 days of exposure, immunocytochemistry revealed an increase in the number of iCT-containing PNE cells. This increase in the number of PNE cells correlated well with the increased iCT content of the lung tissue. We conclude that subchronic cigarette smoke exposure causes an increase in pulmonary levels of iCT and MB, which may be linked to the observed proliferative response of the PNE cells.

Animals↗
PubMed1988

Evidence for cigarette smoke-induced calcitonin secretion from lungs of man and hamster.

In hamsters, acute cigarette smoke inhalation increased serum levels of the hormone calcitonin; and, in humans, smoking of two high-nicotine content cigarettes increased serum and urine levels of this hormone. The source of this immunoreactive calcitonin (iCT) does not appear to be the thyroid gland, since previously thyroidectomized patients demonstrated a similar response. In the hamster, the increased serum iCT levels were accompanied by a decreased lung tissue iCT content and hypocalcemia. It is suggested that the source of the cigarette smoke-induced hypercalcitonemia is the lung, possibly from the iCT-containing pulmonary neuroendocrine (PNE) cells. Moreover, this response appears to be dependent on the nicotine content of the cigarettes.

Animals↗
PubMed1986

Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene.

Small cell lung cancer growing in cell culture possesses biologic properties that allow classification into two categories: classic and variant. Compared with classic small cell lung cancer cell lines, variant lines have altered large cell morphology, shorter doubling times, higher cloning efficiencies in soft agarose, and very low levels of L dopa decarboxylase production and bombesin-like immunoreactivity. C-myc is amplified and expressed in some small cell lung cancer cell lines and all c-myc amplified lines studied to date display the variant phenotype. To investigate if c-myc amplification and expression is responsible for the variant phenotype, a normal human c-myc gene was transfected into a cloned classic small cell lung cancer cell line not amplified for or expressing detectable c-myc messenger RNA (mRNA). Clones were isolated with one to six copies of c-myc stably integrated into DNA that expressed c-myc mRNA. In addition, one clone with an integrated neo gene but a deleted c-myc gene was isolated and in this case c-myc was not expressed. C-myc expression in transfected clones was associated with altered large cell morphology, a shorter doubling time, and increased cloning efficiency, but no difference in L dopa decarboxylase levels and bombesin-like immunoreactivity. We conclude increased c-myc expression observed here in transfected clones correlates with some of the phenotypic properties distinguishing c-myc amplified variants from unamplified classic small cell lung cancer lines.

Animals↗
PubMed1986

Cerebrospinal fluid bombesin and calcitonin in patients with central nervous system metastases from small-cell lung cancer.

To determine whether levels of mammalian bombesin (MB) or calcitonin would be useful in detecting CNS metastases in patients with small-cell lung cancer (SCLC), we measured their concentrations in the CSF of 94 patients who underwent lumbar puncture for suspected CNS involvement. The MB concentration was significantly elevated in the 51 patients with definite CNS metastases as compared with the 30 patients without apparent CNS involvement (P less than .01). This significance was due to increased levels of MB in 18 patients with meningeal carcinomatosis. Whereas CSF MB was detectable (greater than 10 fmol/mL) in only 7% of patients without apparent CNS involvement, CSF MB was detectable in 21% with parenchymal CNS metastases and in 78% of those with meningeal carcinomatosis. Interestingly, 93% of patients having MB concentrations above 20 fmol/mL had meningeal metastases. The calcitonin concentration was significantly elevated in 42 patients with CNS metastases as compared with 27 patients without CNS involvement (P less than .01). Both the 15 patients with meningeal carcinomatosis and the 27 patients with only parenchymal metastases had significantly elevated levels of CSF calcitonin as compared with those without CNS metastases. Fifty-three percent of patients with meningeal carcinomatosis and 48% with parenchymal metastases had a CSF calcitonin level above 18 fmol/mL, whereas only 7% without apparent CNS metastases exceeded this level. Sixty-seven percent of all patients with CNS metastases had increased CSF levels of one of the two hormonal markers. Thus, in SCLC patients, an elevated CSF calcitonin strongly suggested CNS metastases and an elevated MB was very suggestive of the presence of meningeal carcinomatosis. However, only the latter observation seems of clinical importance due to the difficulties in establishing this diagnosis with current diagnostic measures.

Bombesin↗
PubMed1984

Calcitonin as a marker for diethylnitrosamine-induced pulmonary endocrine cell hyperplasia in hamsters.

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.

Animals↗
PubMed1983

Calcitonin secretion by continuous cultures of small cell carcinoma of the lung: incidence and immunoheterogeneity studies.

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.

Animals↗