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Biomedical subjects

E Spindel

Publications and source records attributed to E Spindel.

18 recordsLinked to original sources
PubMed1989

The usefulness of branched chain amino acids in patients with acute or chronic hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with acute liver failure or chronic parenchymal liver disease. It has been hypothesized that changes in protein and amino acid metabolism and catabolism contribute to the pathogenesis of HE. Clinical investigations into the use of branched chain amino acids (BCAA) in the therapy of nutritional support for patients with HE have markedly increased. We have reviewed the rational basis for, and the controversies related to, the use of BCAA in the treatment of HE. We conclude that data on the use of BCAA in HE are controversial. There is marked variation in study design, and often, a lack of appropriate controls in patient numbers, as well as in consistent use of comparable measures of response. The ultimate role for BCAA in the treatment of HE is uncertain and will require additional objective information from well-designed and controlled clinical studies.

Amino Acids, Branched-Chain↗
PubMed1988

Localization of bombesin-like peptides in tumors.

The localization of bombesin gene products in neuroendocrine tumors was achieved by a number of techniques used in combination. These included immunocytochemistry, radioimmunoassay, and chromatographic procedures using a variety of region-specific antibodies recognizing separate portions of probombesin. In situ hybridization using cRNA probes was employed to analyze bombesin gene expression at a cellular level. A novel procedure using a divalent form of bombesin and gold-labeled monoclonal antibodies for the localization of bombesin binding sites at the ultrastructural level was employed in this study. Antibodies to neuron-specific enolase and electron microscopy were employed for the determination of neuroendocrine differentiation. Surgical samples of pulmonary (n = 250) and nonpulmonary (n = 28) small cell carcinomas, 49 carcinoids, and 62 atypical lung carcinoids were investigated and compared with 169 control tumors, including lymphomas, adenocarcinomas, squamous cell carcinomas, and non-small-cell undifferentiated tumors. Cell lines cultured from pulmonary small cell carcinoma and smear preparations of pleural effusions from patients with small cell carcinoma of the lung were also investigated. Strong immunostaining for neuron-specific enolase was noted in all neuroendocrine tumors investigated, and no immunoreactivity was noted in control cases. Electron-dense neurosecretory granules were abundant in carcinoid tumors, scattered in small cell carcinoids, and absent in control cases. Immunostaining for bombesin was particularly strong in benign carcinoids, whereas the more malignant neuroendocrine tumors (e.g., small cell carcinomas) stained best with antibodies to the carboxyl-terminal flanking portion of human probombesin (proGRP). These findings were further validated by radioimmunoassay and chromatography of tissue extracts. Specific binding sites for bombesin were demonstrated on the surface of small cell carcinoma cells maintained in culture. In situ hybridization demonstrated mRNA for preprobombesin in all small cell carcinomas investigated, including surgical samples, cytological preparations, and cell lines. Hybridization reactions varied in intensity, with some cells in autoradiograms almost masked by silver grains and others showing much lighter deposits.

Bombesin↗
PubMed1987

Human gastrin-releasing peptide gene is located on chromosome 18.

Gastrin-releasing peptide (GRP), a bombesin-like peptide, increases plasma levels of gastrin, pancreatic polypeptide, glucagon, gastric inhibitory peptide, and insulin. GRP is produced in large quantities by small-cell lung cancer and acts as a growth factor for these cells. To determine if chromosomal changes in small-cell lung cancer are related to the expression of GRP, we chromosomally mapped the gene using human-mouse somatic cell hybrids. Twenty hybrids, characterized for human chromosomes, were analyzed by Southern filter hybridization of DNA digested with EcoRI. Human DNA cut with EcoRI yields a major band of 6.8 kb and a minor band of 11.3 kb. The 6.8 kb band segregated concordantly with chromosome 18 and the marker peptidase A. The chromosome 3 abnormalities seen in small-cell lung cancer do not correlate with the chromosomal location of GRP, suggesting that the elevated expression of this gene may be due to mechanisms other than chromosomal rearrangement.

Animals↗
PubMed1986

Decision analysis in evaluation of hypergastrinemia.

Hypergastrinemia and gastric acid hypersecretion are the principal laboratory features of Zollinger-Ellison syndrome. Decision and cost-effectiveness analyses were employed in the present study to compare and contrast the diagnostic strategies of initial gastric analysis followed by secretin infusion test versus secretin infusion test alone in the evaluation of hypergastrinemia in patients suspected of having gastrinoma. The results of this study showed that 59 percent of patients with elevated serum gastrin values were either hypochlorhydric or achlorhydric. Application of decision analysis to either diagnostic strategy demonstrated that gastric analysis followed by secretin infusion test, if indicated, was superior in expected value than secretin infusion test alone. Likewise, in this group of patients, performance of gastric analysis in the outpatient setting prior to secretin infusion testing was financially more advantageous than performance of secretin infusion testing alone. These results also demonstrate the importance of performing gastric analysis prior to anticipated hospitalization for evaluation of suspected gastrinoma. Such testing would obviate unnecessary hospitalization and medical costs.

Adolescent↗
PubMed1985

Anaplastic neoplasm in a patient with hairy cell leukemia.

A 63-year-old white man had a history of recurrent pneumonia, pancytopenia, and splenomegaly when the diagnosis of hairy cell leukemia was made on bone marrow biopsy examination. Splenectomy confirmed that diagnosis and his pancytopenia moderately improved. Three years following the diagnosis, the patient developed an upper abdominal mass involving the stomach wall that was found to be an anaplastic "large cell" neoplasm. Palliative radiotherapy was started, but the patient died 2 months later. Cytochemical studies of the anaplastic gastric neoplasm revealed cytoplasmic tartrate resistant acid phosphatase activity. Electron microscopy showed no epithelial differentiation. These observations suggest that the gastric neoplasm represented an evolution of hairy cell leukemia into a more aggressive tumor analogous to the transformation that occurs in other B-cell neoplasms.

Bone Marrow↗
PubMed1984

Action of the methylxanthines on the pituitary and pituitary-dependent hormones.

High doses of caffeine produce a stresslike neuroendocrine response in rats. This response is characterized by increased serum corticosterone, beta-endorphin, and decreased serum growth hormone and TSH. There is no effect on prolactin. Curiously, another common stimulant, amphetamine, produces a similar endocrine response in rats. Like caffeine, amphetamine decreases serum TSH [36], increases serum corticosterone [37], and has little effect on serum prolactin [38]. Perhaps amphetamine and caffeine as stimulants activate the same neurotransmitter systems and hence have similar endocrine effects. In man, typically consumed oral doses of caffeine have little or no endocrine effects. A person must consume 500 mg caffeine (equivalent to 5 cups of coffee) in one sitting for there to be any possible endocrine effects. Under these circumstances the endocrine changes that might occur would be limited to slight elevations in plasma ACTH, beta-endorphin, and cortisol.

Adrenal Glands↗
PubMed1983

The effects of cysteamine on thyrotropin and immunoreactive beta-endorphin secretion in the rat.

We examined the effects of the thiol agent cysteamine (CSH), which is known to deplete the hypothalamus of immunoreactive somatostatin, on physiological TSH and beta- endorphin secretion in the adult male rat. CSH at doses of 90 and 300 mg/kg CSH produced a rapid decline in plasma TSH, whereas a dose of 30 mg/kg did not alter plasma TSH levels. After the higher doses of CSH, TSH levels in the blood remained lower than control values on day 2, but returned to normal by 1 week. This decrease in TSH within the plasma was not associated with a reduction in hypothalamic TRH concentrations. The TSH response to 500 ng/kg TRH was normal in CSH-treated animals. Blockade of norepinephrine synthesis with diethyldithiocarbamate (500 mg/kg) or fusaric acid (100 mg/kg) inhibited TSH secretion in a manner similar to that of CSH. beta-Endorphin-like immunoreactivity (bet-End-LI) was elevated in the plasma immediately after CSH (300 mg/kg) administration. This was associated with a 58% reduction in anterior pituitary beta-End-LI and no change in hypothalmic beta-End-LI. Plasma beta-End-LI returned to normal on day 2. The increase in plasma beta-End-LI induced by immobilization stress was not compromised by CSH treatment. The observed effects of CSH on both TSH and beta-End-LI are consistent with a reduction in central norepinephrine neurotransmission through the known actin of CSH to inhibit dopamine-beta-hydroxylase. Acute stress may play a role as well in the observed changes in TSH and beta-End-LI secretion.

Animals↗
PubMed1983

Neuroendocrine effects of caffeine. II. Effects on thyrotropin and corticosterone secretion.

Caffeine injected i.p. to rats decreased serum thyrotropin and markedly increased serum corticosterone with ED50 values of 40 to 50 mg/kg. Adrenalectomy did not affect the response of thyrotropin to caffeine. Theophylline was as potent as caffeine in inhibiting thyrotropin and stimulating corticosterone secretion; theobromine and paraxanthine were less potent, but their own serum concentrations were also lower. One week of once-daily injections of 50 mg/kg of caffeine produced tolerance to its effects on thyrotropin and corticosterone. The lowest caffeine dose to produce tolerance to a 50-mg/kg challenge dose was 25 mg/kg. Adenosine receptor agonists did not affect serum thyrotropin nor did they block the caffeine-induced decrease in serum thyrotropin. Blockade of the hypothermic effect of caffeine did not alter the effect of caffeine on serum thyrotropin. Similarly, the caffeine-induced decrease in serum thyrotropin was additive to the decrease produced by placing rats in a warm environment or to the increase in serum thyrotropin produced by placing them in the cold. Deviating from the stress-like pattern of increased corticosterone and decreased thyrotropin, caffeine did not affect prolactin secretion in ovariectomized rats with or without estrogen pretreatment.

Adrenalectomy↗
PubMed1981

Characterization of neuropeptides by reversed-phase, ion-pair liquid chromatography with post-column detection by radioimmunoassay. Application to thyrotropin-releasing hormone, substance P, and vasopressin.

Neuropeptide contents of rat brain samples were determined by radioimmunoassay (RIA) after fractionation of tissue extracts by high-performance liquid chromatography (HPLC). Solvent systems were composed of acetic acid, acetonitrile and short-chain (5--8 carbons) alkylsulfonic acids. Separate solvent systems were developed for thyrotropin-releasing hormone, substance P. arginine vasopressin and biologic analogs, and the enkephalins. All separation systems tested gave 80--90% recovery of picogram quantities of peptides. When lyophilized, the HPLC solvents did not interfere significantly with the RIAs, allowing quantitation of tissue concentrations of isolated neuropeptides using the lyophilized eluent from the HPLC. The combination of liquid chromatography with RIA should allow for very accurate identification and quantification of peptides in biologic samples containing large numbers of potentially cross-reacting species of molecules.

Animals↗
PubMed1980

TRH immunoreactivity in rat brain regions, spinal cord and pancreas: validation by high-pressure liquid chromatography and thin-layer chromatography.

Thyrotropin-releasing hormone (TRH) immunoreactivity in rat tissue was assayed using a new reversed-phase, ion-pair, high-pressure liquid chromatography (HPLC) method for separating TRH from its analogs. Virtually all of the TRH immunoreactivity in hypothalamus, brain stem, preoptic area, septum, striatum, frontal cortex, spinal cord and pancreas had chromatographic characteristics corresponding to those of synthetic TRH. When analyzed by two additional, previously described HPLC methods for neuropeptides, all TRH immunoreactivity in rat brain, spinal cord and pancreas also behaved identically to that of authentic TRH. Similarly, in two different thin-layer chromatography systems, all TRH immunoreactivity migrated with that of synthetic TRH. We conclude that TRH-immunoreactive material in rat brain, spinal cord and pancreas really is TRH. The perhaps surprising specificity of the TRH immunoassay may occur because antibodies directed against TRH (pyroglutamyl-histidyl-prolineamide) recognize two atypical amino acids in close proximity.

Animals↗
PubMed1980

Effects of caffeine on anterior pituitary and thyroid function in the rat.

We studied the effects of acute, intraperitoneal administration of caffeine on serum thyrotropin (TSH), growth hormone, prolactin, thyroxine and 3,3',5-triiodothyronine in rats. Caffeine lowered serum TSH and GH in a dose-dependent manner with ED50 values of 30 and approximately 50 mg/kg, respectively. TSH levels were depressed 1 to 6 hr after injection and correlated with serum caffeine levels greater than 20 micrograms/ml. The decrease in serum TSH was followed by decreases in serum 3,3',5-triiodothyroxine and thyroxine 4 hr after caffeine administration. Theophylline and theobromine had effects similar to those of caffeine on hormone levels. Caffeine did not significantly affect hormone secretion when incubated directly with rat pituitaries in vitro. Administration of antisomatostatin antiserum to rats blocked the inhibitory effects of caffeine on serum GH levels, suggesting that caffeine inhibits GH and TSH secretion by releasing hypothalamic somatostatin.

Animals↗