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Biomedical subjects

L Gaspar

Publications and source records attributed to L Gaspar.

51 records · Page 3Linked to original sources
PubMed1987

Characterization of N-terminal fragment of proopiomelanocortin in cerebrospinal fluid.

The molecular forms of the N-terminal fragment (hNT) of proopiomelanocortin were studied in cerebrospinal fluid (CSF) from normal subjects, methadone-addicted patients, patients with hydrocephalus, and a patient with Nelson's syndrome. The peptides were characterized by molecular sieving and Concanavalin A-Sepharose chromatography. Immunoreactivity was detected using antibodies directed against the N- and C-terminal portions of the hNT (hNT and gamma 3MSH antibodies, respectively). The mean immunoreactive hNT (IR-hNT) levels in samples of CSF from normal subjects, patients with hydrocephalus, methadone addicts, and the patient with Nelson's syndrome were 410 +/- 158 (+/- SE), 435 +/- 137, 328 +/- 183, and 85,700 pg/mL, respectively. Molecular sieving chromatography revealed one predominant species of IR-hNT and/or gamma 3MSH which coeluted with the authentic hNT-(1-76) marker. However, 10-16% of the total immunoreactivity eluted close to the void volume. No significant differences in the elution profiles were found among these groups. Most (61-69%) of the IR-hNT bound to Concanavalin A, and the elution patterns of samples from this column were similar to that of purified hNT-(1-76). These results support the view that the major molecular form of hNT in CSF is NT-(1-76) as it is in the pituitary gland.

Adolescent↗
PubMed1985

Pro-opiomelanocortin-related peptides in cerebrospinal fluid: a study of manic-depressive disorder.

Five peptide fragments of pro-opiomelanocortin (alpha-melanocyte-stimulating hormone, beta-lipoprotin, adrenocorticotropic hormone, beta-endorphin, and the N-terminal fragment of pro-opiomelanocortin) were measured by radioimmunoassay in cerebrospinal fluid (CSF) and plasma from 31 normal volunteers and 26 euthymic lithium-treated bipolar patients (14 of whom provided a second CSF sample in the unmedicated state). With the exception of alpha-melanocyte-stimulating hormone, in the normal volunteers' CSF, levels of these peptides were highly correlated with one another, suggesting that: (1) some common regulatory factor may control the levels of these four peptides in CSF; and (2) CSF alpha-melanocyte-stimulating hormone is independently regulated from the other pro-opiomelanocortin products. Some of these correlations were absent in the patient groups, suggesting subtle alterations in pro-opiomelanocortin processing in manic-depressive illness. No effect of lithium on the CSF levels of these peptides was observed. No group differences were found.

Adrenocorticotropic Hormone↗
PubMed1985

Characterization of peptides derived from pro-opiomelanocortin in the biological fluids of a patient with Nelson's syndrome.

Molecular forms of immunoreactive adrenocorticotropin (ACTH), beta-lipotropin (beta-LPH) (beta-endorphin (beta-END), human NH-2-terminal (hNT) of pro-opiomelanocortin (POMC), and gamma-3-melanotropin (gamma-3-MSCH) were studied in plasma, CSF and urine of a patient with Nelson's syndrome by molecular sieving and concanavalin A (Con A)-sepharose chromatography. In the culture tumor medium of the tumor cells, and in the plasma and CSF, these compounds were found mainly in forms corresponding in molecular weight to the authentic peptides, with the exception of gamma-3-MSH. Stimulation of the pituitary tumor by synthetic ovine corticotropin-releasing factor (CRF 1-41) caused a 171-468% increase in vivo (60 min) and 453-953% increase in vitro (3h incubation) in the levels of POMC derived peptides; it increased the relative amount of beta-END in vivo, and that of beta-LPH in vitro. Molecular sieving chromatography of urine samples revealed that beta-LPH and hNT are extensively degraded by the kidney. By contrast, ACTH showed no significant renal degradation before the removal of the pituitary adenoma. However, following pituitary surgery, only smaller fragments of immunoreactive (IR) ACTH were detected in the urine. These results suggest no major abnormal metabolic pathway for POMC in Nelson's syndrome, although the proportions of various peptides derived from the precursor could be different in vivo from those after in vitro incubation under basal conditions and during CRF stimulation. The results also indicate differences in the renal handling of ACTH in POMC hypersecretory states.

Adrenocorticotropic Hormone↗
PubMed1984

Urinary molecular forms of human N-terminal of proopiomelanocortin: possible deglycosylation and degradation by the kidney.

The NH2-terminal fragment (hNT) of proopiomelanocortin is found predominantly as one molecular form of apparent mol wt of 12K in the circulation. Since the kidney may play an important role in the elimination and degradation of proopiomelanocortin-related peptides, we analyzed the urinary forms of immunoreactive hNT (IR-hNT) by molecular sieving and carbohydrate affinity (Concanavalin A-agarose) chromatography. RIA specific for the amino terminal portion and for the gamma 3-MSH (carboxy-terminal portion of hNT) were used in these studies. Molecular sieve chromatography revealed several forms of IR-hNT in the urine from normal subjects, patients with Nelson's syndrome, and patients with ectopic ACTH-secreting tumors. A considerable decrease in IR-hNT and IR-gamma 3-MSH was found in the urine of a patient with ACTH deficiency and normal subjects during glucocorticoid suppression. In urine from normal subjects and a patient with lung cancer not causing Cushing's syndrome, the majority of amino-terminal IR-hNT (66-83%) had apparent mol wts of 3-4K, 6-7K, and 8-10K, and did not cross-react with the gamma 3-MSH antiserum. Ten to nineteen percent of the total IR-hNT was eluted in the position of authentic hNT and reacted with the gamma 3-MSH RIA. In patients with Nelson's syndrome and those with ectopic ACTH syndrome, almost no intact hNT (less than 7% of the total) was present in urine; most of the IR-hNT appeared in the elution volumes with an apparent mol wt of 8-10K. In addition, smaller forms (6-7K and 3-4K) of hNT were also detected in the urine of these patients. The major form of urinary IR-gamma 3-MSH exhibited an apparent mol wt of 7-8K and did not correspond to any of the peaks of IR-hNT. Carbohydrate affinity chromatography (Concanavalin A-agarose) of smaller forms of IR-hNT revealed weak affinity to the lectin, which suggests loss of the carbohydrate moiety during renal excretion. We conclude that hNT in urine is present in extensively cleaved forms and that deglycosylation may be an important step in hNT degradation. These results support a role for the kidney in the catabolism of hNT.

ACTH Syndrome, Ectopic↗
PubMed1984

Synergistical effects of ovine corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) on the release of pro-opiomelanocortin (POMC) related peptides by pituitary adenoma of a patient with Nelson's syndrome in vitro.

The effects of synthetic ovine corticotropin-releasing factor (oCRF), arginine vasopressin (AVP), alpha-melanocortin (alpha MSH), and dexamethasone on the release of pro-opiomelanocortin (POMC)-related peptides were studied on a pituitary adenoma of a patient with Nelson's syndrome. CRF, at doses up to 100 ng/ml, has no effect on IR-ACTH, IR-hNT or IR-beta LPH secretion by the pituitary adenoma cells within the first week of monolayer culture. During the second week of in vitro conditions, however, the cells responded to oCRF (1-100 ng/ml) with a significant increase in all three POMC-related peptides. AVP (10 and 100 ng/ml) was effective in stimulating secretion of the three POMC-related peptides on day 6 in vitro; in addition, during the second week in culture, AVP (1 ng/ml) acted synergistically with 1-100 ng/ml of oCRF to release IR-ACTH, IR-hNT and IR-beta LPH at least 3-4 fold higher than CRF alone. alpha MSH (10 micrograms/ml) and dexamethasone (10(-6)M) did not alter the release of any of the three peptides. These results demonstrate that CRF and AVP can act synergistically on human pituitary tissue in vitro to promote the release of POMC-related peptides and also in vivo as shown by others.

Adenoma↗
PubMedDate not supplied

cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases.

Based on the concept of sequence conservation around the active sites of serine proteinases, polymerase chain reaction applied to mRNA amplification allowed us to obtain a 260-bp probe which was used to screen a mouse pituitary cDNA library. The primers used derived from the cDNA sequence of active sites Ser* and Asn* of human furin. Two cDNA sequences were obtained from a number of positive clones. These code for two similar but distinct structures (mPC1 and mPC2), each being homologous to yeast Kex2 and human furin. In situ hybridization (mPC1) and Northern blots (mPC1 = 3.0 kb and mPC2 = 2.8 and 4.8 kb) demonstrated tissue and cellular specificity of expression, only within endocrine and neuroendocrine cells. These data suggest that mPC1 and mPC2 represent prime candidates for tissue-specific pro-hormone converting proteinases.

Amino Acid Sequence↗
PubMedDate not supplied

[Effectiveness of radiotherapy in non-resectable cavernous hemangioma of the liver].

In the management of the unresectable cavernous hemangioma of the liver, the Radiotherapy has an important role. This paper reports the experience of Radiotherapy department of Hospital Santa Maria. The authors review retrospectively the literature concerning techniques, results and complications of this therapy and analyse other possible attitudes in treatment of these lesions.

Adult↗