The effectiveness of synthetic salmon calcitonin (SCT) administered as a nasal spray was assessed via clinical, biological, and radiological variables in 17 previously untreated Pagetic patients over a 1-year course of therapy. The results showed a highly significant decrease of serum alkaline phosphatase (S-ALP) (p less than 0.05 after 1 month of treatment) and of the urinary hydroxyproline/creatinine ratio (OH/Cr) (p less than 0.01 after 1 month of treatment). For the whole group, the mean decrease in S-ALP was 37 +/- 4% (SEM) after 6 months (p less than 0.01) and 31 +/- 5% after 1 year (p less than 0.01). The mean fall in OH/Cr was 35 +/- 6% (SEM) (p less than 0.01) and 37 +/- 7% (p less than 0.01) after 6 and 12 months, respectively. None of the usual side-effects of SCT were reported and local tolerance was excellent throughout the study.

Administration, Intranasal↗

PubMed1988

Evidence that the phagocytosis mediated by the peanut agglutinin-like activity of IgG(Fc) receptors of human monocytes is selectively modulated by estradiol and natural estrogens.

The percentage of human monocytes (MCs) that are able to form rosettes with, and to phagocytose, IgG-coated sheep red blood cells (IgG-SRBCs) has been first determined in vitro by a classical rosette assay in 12 postmenopausal (PM) women. Half of them never received any suppletive estrogen (E) therapy at the time of testing, whereas the other six were chronically treated with E. Three different preparations of the same anti-SRBC IgG antibody batch were coated to SRBCs: the first one was the starting antibody preparation [IgG(total] and the other two were purified by affinity chromatography either on Sepharose-concanavalin A (Con A) or on agarose-peanut agglutinin (PNA) columns specifically recognizing terminal, and/or accessible, alpha-mannosyl [IgG(Con A)] or beta-galactosyl [IgG(PNA)] residues of the Fc domain, respectively. The three IgG preparations exhibited similar hemagglutinating antibody titers (1/100). All experiments were conducted using a coating range of 5000 to 6000 IgG antibody molecules per SRBC. In PM women with E, the rosetting capacity of autologous MCs (percentage of MCs rosetting at least three IgG-SRBCs), their phagocytosing capacity (percentage of MCs ingesting at least three IgG-SRBCs), and the phagocytosis index (number of SRBCs ingested/100 MCs) were similar for each IgG-SRBC preparation considered. In contrast, in PM women without E, the capacity of MCs to phagocytose IgG(PNA)-SRBCs, as well as the phagocytosis index measured with those SRBCs, was strongly reduced (P less than 0.01 at least), when compared to the same parameters determined using IgG(total)-SRBCs and IgG(Con A)-SRBCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Influence of the nature of calcium salts on serum calcium, phosphorus, calcitonin, growth hormone, and somatomedin C.

Twenty healthy males were randomly divided into three groups. Each subject received either 405 mg elemental calcium (Ca) as a salt linked to an amino acid precursor, 405 mg CaC12 or 1000 mg Ca as Ca gluconolactate and carbonate. In all three cases, Ca intake led to an increase of serum Ca and TCT production and a decrease of PTH liberation. However, when Ca is linked to the amino acid precursor, an elective stimulation of growth hormone (GH) and somatomedin C (SmC) occurs. Due to the nature of its amino acid precursor, this salt seems to stimulate GH and SmC liberation through hypophysis. This could be a major pathway in decoupling of the sequence resorption-formation and therapy of metabolic bone diseases.

Adult↗

PubMed1988

Characterization of proteoglycans produced by human chondrocytes cultivated in clusters.

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Cartilage↗

PubMed1988

Epithelial membrane antigen (EMA) distribution in various biological fluids.

Different human biological fluids, namely breast cyst fluids (five), milks (four), sera (five), were submitted to molecular sieving chromatography on Sepharose CL6B. Global protein contents of the eluted fractions were estimated by the Bradford method. Epithelial membrane antigen (EMA) was assayed by two different ELISA techniques using polyclonal and monoclonal antibodies. Various molecular species reacting with EMA (15) were found in the chromatographies with molecular weights ranging from 35 to 1500 kd. But the total amount of antigens detected using polyclonal or monoclonal antibodies was quite similar. Moreover no significant difference was found between the sera from two lactating women and the sera from three women with adenocarcinoma with respect to the molecular distribution of different molecular species of EMA.

Adenocarcinoma↗

PubMed1988

Breast gross cystic disease protein 15 in human breast cancer in culture.

Media from explants of 120 human breast cancers cultured for 24 h were analysed for breast gross cystic disease protein 15 (GCDFP-15). The protein was detected in media from 94 tumours (73%) in concentrations varying from 1.5 to 2100 ng/ml. Levels were not related to menopausal status of the patient, disease stage, tumour oestrogen receptors or the derivation of tumour material. However, concentrations were significantly related to the degree of apocrine differentiation of the tumour and, in a subset of the cancers, capacity to release GCDFP-15 was positively correlated with incidence of progestogen and androgen receptors. There was also a negative quantitative correlation between production of GCDFP-15 and glycoprotein hormone alpha subunit (but no relationship with CEA). In 10 tumours culture was continued for 48 h. Values for GCDFP-15 were always considerably lower in the 24-48 h media compared with those from 0-24 h and cytosols from post-culture explants contained no detectable GCDFP-15. In contrast, CEA levels were often comparable in 0-24 and 24-48 h media and explants after culture frequently contained substantial amounts of CEA. The high proportion of breast carcinomas producing GCDF-15 in relatively large amounts and its rapid release make it an interesting marker by which the in vitro activity of human breast cancers may be monitored.

Apolipoproteins↗

PubMed1988

Biological and clinical assessment of a new bisphosphonate, (chloro-4 phenyl) thiomethylene bisphosphonate, in the treatment of Paget's disease of bone.

Several Biophosphonates have been used as therapeutic agents for Paget's bone disease. (Chloro-4 phenyl)thiomethylene-bisphosphonate (CIPsMBP) has recently been shown to have significant antiosteoclastic activity while an affect of CIPsMBP on mineralization was only observed at high doses. We tested this drug for 6 months in 23 pagetic patients distributed in three groups. Gr 1 (n = 5) receiving 200 mg/day showed a decrease of serum alkaline phosphatase (SAP) to 42 +/- 4% (p less than 0.01) of initial value (100%) while hydroxyprolinuria/creatinuria ratio (OH/Cr) dropped to 69 +/- 8% of baseline. In 4 patients receiving 400 mg/day, SAP improved to 48 +/- 9% of initial value (p less than 0.01) and OH/Cr to 40 +/- 3% (p less than 0.01). In the last group (n = 14) receiving 200 mg/day for 3 months, and 400 mg/day thereafter up to the 6th month SAP decreased to 53 +/- 4% and OH/Cr to 62 +/- 6% of initial value (p less than 0.01). Clinical improvement was significant from the first month of treatment. No resistance (mean decrease of SAP lower than 30%) was recorded and no radiological or clinical evidence of mineralization defect appeared. The clinical and biological tolerance was excellent throughout the study.

Aged↗

PubMed1988

Endocrine, paracrine and autocrine control of follicular development.

Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to prevent other follicles from developing at the same time as dominant follicle. These other follicles remain quiescent or evaluate to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of estrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching metaphase of the second meiotic division. Several factors are involved in the inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin and oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells.

Endocrine Glands↗

PubMed1988

The neurohormonal thymic microenvironment: immunocytochemical evidence that thymic nurse cells are neuroendocrine cells.

Thymic neuroendocrine cells were identified by immunofluorescence in the murine thymus through the use of monoclonal antibody A2B5, and specific polyclonal antisera against neurophysin (NP), oxytocin (OT) and arginine vasopressin (AVP). Two reactive regions were clearly identified: the subcapsular cortex and the medulla. A close correspondence was observed between A2B5-reactive and NP-immunoreactive cells in the medulla. An important epithelial population of the subcapsular cortex, the thymic nurse cells (TNCs), were found to be A2B5-positive and to contain immunoreactive NP, OT and AVP. The neuroendocrine nature of TNCs was further substantiated by their high reactivity with an antiserum against neuron-specific enolase. These observations demonstrate the presence in the thymus gland of an original neuroendocrine microenvironment which could be of functional importance in the mediation of central influences upon T lymphocyte differentiation.

Animals↗

PubMed1988

Effect of diclofenac on plasma levels of immunoreactive prolactin, follicle stimulating hormone, luteinizing hormone, thyrotropin, and beta-endorphin in humans.

Prostaglandins have been shown to modulate the secretion of several pituitary hormones, suggesting that therapeutic doses of nonsteroidal anti-inflammatory drugs may change basal hormone levels. In this study, plasma levels of prolactin, follicle stimulating hormone, luteinizing hormone, thyrotropin and beta-endorphin were determined in 6 healthy men after administration of diclofenac, a prostaglandin synthesis inhibitor. The subjects were given 75 mg intramuscularly and 50 mg orally at 08.00 h the first day, 50 mg orally at 08.00, 12.00 and 20.00 h the second day and an additional 50 mg orally at 08.00 h the third day. Blood samples were collected throughout these 3 days. Diclofenac resulted in a significant and sustained decrease in plasma level of prolactin (p less than 0.005). The other hormones did not demonstrate significant change following diclofenac administration. These data suggest that administration of a prostaglandin synthesis inhibitor, such as diclofenac, selectively alters basal pituitary secretion of prolactin in humans without a detectable effect on plasma levels of other pituitary hormones. This study supports the hypothesis that prostaglandins are necessary for maintaining basal level of prolactin secretion in man.

Adult↗

PubMed1988

Altered metabolic and hormonal responses to epinephrine and beta-endorphin in human obesity.

Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and beta-endorphin (both in doses of 15, 50, and 80 ng/kg.min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, less than 25 kg/m2) and obese (body mass index, greater than 30 kg/m2) subjects. Fasting plasma insulin, C-peptide, and beta-endorphin concentrations were significantly higher in the obese than in the normal subjects (P less than 0.01-0.005). In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of beta-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and beta-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 +/- 370 pg/min.mL (ng/min.L); sum of single effects, 750 +/- 152 (+/- SE) pg/min.mL (ng/min.L); P less than 0.01]. The plasma epinephrine [207 +/- 21, 607 +/- 70, and 1205 +/- 134 pg/mL (1130 +/- 115, 3640 +/- 382, and 6577 +/- 691 pmol/L] and beta-endorphin [875 +/- 88, 1250 +/- 137, and 1562 +/- 165 pg/mL (250 +/- 25, 358 +/- 39, and 447 +/- 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion. In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, beta-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and beta-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1988

Identification of vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate secretion of antidiuretic hormone and an oat cell carcinoma.

In this study we have identified and characterized several vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion and oat cell carcinoma of the lung. Immunoreactive plasma vasopressin was measured after gel filtration (Sephadex G-25) or C-18 cartridge extraction using two different region-specific antisera: AS1 and AS2. Antiserum AS1 is more specifically directed towards the antigenic site of the hexapeptidic ring of arginine-vasopressin (AVP), whereas AS2 is more specifically directed towards the C-terminal region of AVP. Unexpectedly, the Sephadex G-25 gel filtration elution profile of the immunoreactive vasopressin was very heterogeneous, indicating the presence of several molecular species. After extraction of total AVP and AVP-like peptides of this plasma, an unusual AS1/AS2 ratio of immunoreactivity was observed, suggesting the presence of vasopressin-like peptides which differ from AVP in the C-terminus.

Aged↗

PubMed1988

Production of tumour necrosis factor-alpha, interferon-gamma and interleukin-2 by peripheral blood mononuclear cells of subjects suffering from rheumatoid arthritis.

Using radio-immunoassay methods, the production of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) released by peripheral blood mononuclear cells (PBMC), maintained in culture and stimulated by phytohemagglutinin (PHA), was measured in normal subjects and patients with active or inactive rheumatoid arthritis (RA). Results indicated a dissociation between mitogenic response and secretion of mediators by PBMC under the influence of PHA in both normal controls and in patients with rheumatoid arthritis (RA). While [3H]thymidine incorporation was characterized by a rather bell-shaped curve with increasing concentrations of PHA, IL-2 and TNF-alpha displayed a linear dose-dependent increase. [3H]thymidine uptake by PBMC was in the same range in normal subjects as in patients with active and inactive RA, although cytokine secretion differed. The PBMC of patients with active RA produced less TNF-alpha, IL-2, and IFN-gamma than did those of the controls. In cases of inactive RA, the secretory response varied from subject to subject; mean values did not differ from those of normal subjects, except for those of IL-2 (p less than 0.01). The significance and the clinical relevance of these findings are discussed.

Adult↗

PubMed1988

Is there any place for salmon calcitonin in prevention of postmenopausal bone loss?

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Animals↗