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T Lucas

Publications and source records attributed to T Lucas.

At least 19 recordsLinked to original sources
PubMed2000

Chemosensitisation of malignant melanoma by BCL2 antisense therapy.

BACKGROUND: Chemoresistance of malignant melanoma has been linked to expression of the proto-oncogene BCL2. Antisense oligonucleotides (ASO) targeted against BCL2 mRNA decreased BCL2 protein concentrations, increased tumour-cell apoptosis, and led to tumour responses in a mouse xenotransplantation model when combined with systemic dacarbazine. This phase I-II clinical study investigated the combination of BCL2 ASO (augmerosen, Genasense, G3139) and dacarbazine in patients with advanced malignant melanoma expressing BCL2. METHODS: In a within-patient dose-escalation protocol, 14 patients with advanced malignant melanoma were given augmerosen intravenously or subcutaneously in daily doses of 0.6-6.5 mg/kg plus standard dacarbazine treatment (total doses up to 1000 mg/m2 per cycle). Toxicity was scored by common toxicity criteria. Plasma augmerosen concentrations were assayed by high-performance liquid chromatography. In serial tumour biopsy samples, BCL2 protein concentrations were measured by western blotting and tumour-cell apoptosis was assessed. FINDINGS: The combination regimen was well tolerated, with no dose-limiting toxicity. Haematological abnormalities were mild to moderate. Lymphopenia was common, but no febrile neutropenia occurred. Higher doses of augmerosen were associated with transient fever. Four patients had liver-function abnormalities that resolved within 1 week. Steady-state plasma concentrations of augmerosen were attained within 24 h, and increased with administered dose. By day 5, daily doses of 1.7 mg/kg and higher led to a median 40% decrease in BCL2 protein in melanoma samples compared with baseline, concomitantly with increased tumour-cell apoptosis, which was greatly increased after dacarbazine treatment. Six patients have shown antitumour responses (one complete, two partial, three minor). The estimated median survival of all patients now exceeds 12 months. INTERPRETATION: Systemic administration of augmerosen downregulated the target BCL2 protein in metastatic cancer. Such downregulation of BCL2, combined with standard anticancer therapy, offers a new approach to the treatment of patients with resistant neoplasms.

Adult↗
PubMed2000

Expression and function of sialoadhesin in rat alveolar macrophages.

Alveolar macrophages (Amφ) represent an immunologically distinct sub-population within the reticuloendothelial system. Phagocytosis and possibly antigen presentation by Amφ are essential components of specific and innate primary immune defence processes against inhaled material. The mφ-restricted sheep erythrocyte receptor sialoadhesin (Sn) is a member of the immunglobulin superfamily and binds specifically to sialic acid-containing structures such as selectins and was originally identified as the sheep erythrocyte receptor (SER) responsible for sialic acid-dependent binding of native sheep erythrocytes (SE) to resident murine bone marrow macrophages in rosetting assays. Sn expression has been demonstrated on murine and rat mφ in lymphatic organs and is recognised by the monoclonal antibody (mAb) ED3 in the rat. In addition, sialic acid-dependent receptor (SAR) activities that mediate rosette formation of alveolar, peritoneal, splenic and bone marrow-resident rat mφ with SE pretreated with gangliosides and SER-like activities between native SE and trypsinised Amφ, have been described. The binding activities of both SAR and Sn show similar characteristics suggesting that these molecules are closely structurally related or identical. To clarify the relationship between Sn, SAR and SER-like activities, the binding of mAb ED3 to isolated rat Amφ was investigated by flow cytometry and rosetting assays. It is demonstrated that rat Amφ express Sn and evidence is provided that SAR and SER-like activities are mediated by Sn.

Animals↗
PubMed2000

The ETV6-NTRK3 gene fusion encodes a chimeric protein tyrosine kinase that transforms NIH3T3 cells.

The congenital fibrosarcoma t(12;15)(p13;q25) rearrangement splices the ETV6 (TEL) gene on chromosome 12p13 in frame with the NTRK3 (TRKC) neurotrophin-3 receptor gene on chromosome 15q25. Resultant ETV6-NTRK3 fusion transcripts encode the helix - loop - helix (HLH) dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. We show here that ETV6-NTRK3 homodimerizes and is capable of forming heterodimers with wild-type ETV6. Moreover, ETV6-NTRK3 has PTK activity and is autophosphorylated on tyrosine residues. To determine if the fusion protein has transforming activity, NIH3T3 cells were infected with recombinant retroviral vectors carrying the full-length ETV6-NTRK3 cDNA. These cells exhibited a transformed phenotype, grew macroscopic colonies in soft agar, and formed tumors in severe combined immunodeficient (SCID) mice. We hypothesize that chimeric proteins mediate transformation by dysregulating NTRK3 signal transduction pathways via ligand-independent dimerization and PTK activation. To test this hypothesis, we expressed a series of ETV6-NTRK3 mutants in NIH3T3 cells and assessed their transformation activities. Deletion of the ETV6 HLH domain abolished dimer formation with either ETV6 or ETV6-NTRK3, and cells expressing this mutant protein were morphologically non-transformed and failed to grow in soft agar. An ATP-binding mutant failed to autophosphorylate and completely lacked transformation activity. Mutants of the three NTRK3 PTK activation-loop tyrosines had variable PTK activity but had limited to absent transformation activity. Of a series of signaling molecules well known to bind to wild-type NTRK3, only phospholipase-Cgamma (PLCgamma) associated with ETV6-NTRK3. However, a PTK active mutant unable to bind PLCgamma did not show defects in transformation activity. Our studies confirm that ETV6-NTRK3 is a transforming protein that requires both an intact dimerization domain and a functional PTK domain for transformation activity. Oncogene (2000) 19, 906 - 915.

3T3 Cells↗
PubMed2000

Efficacy of a steroid nasal spray compared with an antihistamine nasal spray in the treatment of perennial allergic rhinitis.

Allergic rhinitis is a common disease with a lifetime prevalence of 20% among the United States population. The cost of medication alone to manage allergic rhinitis in the United States was estimated to be $3.1 billion. The two most commonly prescribed classes of medications are antihistamines and topical nasal steroids. The data on comparing the efficacy of a commonly used antihistamine (azelastine hydrochloride) with that of topical steroids, however, are conflicting. Therefore, the reported study was undertaken to determine the efficacy of azelastine with that of a topical nasal steroid (flunisolide) in treating patients for the symptoms of perennial allergic rhinitis. Forty-four subjects were enrolled in a double-blind, placebo-controlled study using Balaam's design. In one group, patients were treated with topical nasal corticosteroids or placebo. In the other group, patients were treated with the antihistamine nasal spray or placebo. Subjective data were collected by the use of questionnaires and a daily diary, which focused on nasal symptoms, sleep, and daytime sleepiness. The results demonstrated that the topical nasal corticosteroid performed superiorly to the antihistamine nasal spray in improving sleep, daytime sleepiness, sneezing, ocular and nasal pruritus, and nasal congestion. Thus, the topical nasal corticosteroid was found to be more effective than antihistamine nasal spray in reducing symptoms of allergic rhinitis. This study provides further support for the use of topical nasal corticosteroids as first-line treatment for perennial allergic rhinitis.

Administration, Intranasal↗
PubMed1999

Self-renewal, maturation, and differentiation of the rat myelomonocytic hematopoietic stem cell.

Hematopoiesis is viewed as a differentiating system emanating from a pluripotent hematopoietic stem cell capable of both self-renewal and differentiation. By identifying and characterizing a novel and highly specific in vitro mitogenic response to the N-acetyl glucosamyl/sialic acid specific, stem cell-binding lectin wheat germ agglutinin (WGA), we demonstrate the existance of a rare (0.1%), plastic adherent precursor in rat bone marrow capable of proliferation (two to seven divisions) in response to WGA. Stimulated cells possess a lineage (lin)low/- immunophenotype and immature blastoid morphology (WGA blasts). A subsequent proliferative response to stem cell factor (SCF), the ligand for the proto-oncogene receptor tyrosine kinase c-kit, is characterized by an initial maturation in immunophenotype and subsequent self-renewal of cells (SCF blasts) without differentiation for at least 50 generations. Although granulocyte colony-stimulating factor (G-CSF), interleukin (IL) -6, IL-7, and IL-11 synergize with SCF to increase blast colony formation, cytokines such as granulocyte-macrophage CSF or IL-3 are without significant effect. At all time points in culture, however, cells rapidly differentiate to mature neutrophils with dexamethasone or to mainly monocytes/macrophages in the presence of 1alpha,25-dihydroxyvitamin D3, characterized by cell morphology and cytochemistry. Removal of SCF during blast maturation, self-renewal, or induction of differentiation phases results in apoptotic cell death. Data indicate a pivotal role for SCF/c-kit interaction during antigenic maturation, self-renewal, and apoptotic protection of these lineage-restricted progenitors during non-CSF-mediated induction of differentiation. This approach provides a source of many normal, proliferating myelomonocytic precursor cells, and introduces possible clinical applications of ex vivo expanded myeloid stem cells.

Animals↗
PubMed1998

Effects of dental amalgam and heavy metal cations on cytokine production by peripheral blood mononuclear cells in vitro.

The effects of dental amalgam on cytokine production by human peripheral blood mononuclear cells (PBMC) from healthy donors were analyzed. To induce cytokine production, PBMC were stimulated with lipopolysaccharide, phytohemagglutinin, or staphylococcal enterotoxin A and cultured for 48 h in the presence of either freshly prepared amalgam, aged amalgam, or amalgam-conditioned culture medium (ACCM). The concentrations of several cytokines were measured in PBMC supernatants by enzyme-amplified sensitivity immunoassays (EASIAs). Freshly prepared amalgam as well as ACCM induced a decrease in the production of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10), and an increase in the concentrations of tumor necrosis factor-alpha (TNF-alpha). Both fresh amalgam and ACCM showed no effects on IL-2, IL-6, or granulocyte-macrophage colony-stimulating factor levels. Amalgam aged for 6 weeks did not affect the concentration of any of the above cytokines. To investigate which heavy metal cations released from amalgam caused the observed immunomodulatory effects, Cu2+, Hg2+, and Sn2+, which were detected in amalgam supernatants by inductively coupled plasma atomic spectrophotometry, were added as salts to the cultures. Cu2+ and Hg2+ induced a decrease in IFN-gamma and IL-10 levels, and Hg2+ an increase in TNF-alpha concentrations. Cytokine production was not significantly modulated by Sn2+. Under these experimental conditions, release of Ag+ into culture medium was not detectable. However, Ag+ markedly suppressed the production of IFN-gamma, IL-10, and TNF-alpha. In summary, our results show that fresh amalgam, but not amalgam aged for 6 weeks, causes changes in the cytokine pattern of PBMC in vitro, and that these effects are due to the release of Cu2+ and Hg2+.

Cations↗
PubMed1998

Cytotoxic effects of dental composites, adhesive substances, compomers and cements.

OBJECTIVES: Although research interest in biocompatibility of dental materials has been increasing, findings are frequently controversial and non-harmonized experimental approaches often lead to the production of contradictory results. The aim of this study was to compare the cytotoxic effects of six different light-cured dental composites, one compomer, one advanced glass-ionomer, two glass-ionomer cements, two zinc phosphate cements, one calcium hydroxide liner, one composite cement and one carboxylate cement with the same standardized cell-culture system. Two composites, one compomer and one advanced glass-ionomer were also tested in combination with the appropriate bonding substances and surface primers. METHODS: Specimens were added to the cultures immediately after production or after preincubation for 1, 2 or 7 days or 6 weeks under cell-culture conditions. Specimens were incubated with L-929 fibroblasts for 72 h and cell numbers determined by flow cytometry. RESULTS: All freshly prepared composite materials were cytotoxic. These effects diminished with increased preincubation times and were not significant after 7 days. Combinations of composites and bonding substances were still cytotoxic after preincubation for 7 days, but not after 6 weeks. Combinations of compomers and bonding substances demonstrated stronger toxicity than composites, although these effects were reduced earlier during preincubation. Glass-ionomer and phosphate cements showed similar effects to the composites with the exception of carboxylate cement, which demonstrated severe and persistent effects even after 6 weeks' preincubation. Together, our data provide evidence that all dental materials tested are cytotoxic immediately after production and that these effects are reduced after different preincubation periods in most cases. SIGNIFICANCE: Tested with a standardized cell-culture system, differences in toxicological potency between various commonly used dental materials were observed. Cytotoxicity data from standardized protocols should form the basis of screening the cytotoxic effects of new materials.

Adhesives↗
PubMed1998

Growth hormone secretory response to intravenous galanin infusion in acromegalic patients.

Galanin is a 29-amino acid neuropeptide which stimulates the secretion of growth hormone (GH) in normal men. Although the diagnosis of acromegaly involves demonstrating hypersecretion of GH and/or abnormalities in GH secretory dynamics, sometimes it is difficult to establish the activity of the disease. The aim of our study was to assess the response to galanin infusion in acromegalic patients (active and cured). We studied 19 subjects: 5 healthy volunteers (group I), 9 patients with active acromegaly (group II), and 5 with acromegaly cured after transsphenoidal surgery (group III). We performed a test of infusion with porcine galanin (8 microg/Kg/h) to study the secretory response of the GH. Galanin produced a marked increase in GH in the controls, group I (F9,36 = 5.34; p < 0.01) and in the cured patients, group III (F9,36 = 7.35; p < 0.01). On the other hand, galanin did not significantly modify the secretion of GH in the patients with active disease, group II. The areas under the curve (AUC) were higher in groups I and III compared to group II (p < 0.01). Nevertheless, there were no statistically significant differences in the AUC of groups I and III. Our results indicate that the differences in the GH response to galanin in patients with active and cured acromegaly could be of value in the study of the disease.

Acromegaly↗
PubMed1997

The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease.

BACKGROUND: Irradiation of the pituitary is widely considered the most appropriate treatment for patients with Cushing's disease in whom transsphenoidal microsurgery has been unsuccessful. However, there is little information about the long-term efficacy of this treatment. METHODS: We used external pituitary radiation to treat 30 adult patients with persistent or recurrent Cushing's disease after unsuccessful transsphenoidal surgery. The mean (+/-SD) dose of radiation was 50+/-1 Gy. Pituitary and adrenal function was assessed every six months after radiation therapy. Remission was defined as the regression of symptoms and signs of Cushing's syndrome, normal urinary cortisol excretion, and a low plasma cortisol concentration in the morning after the administration of 1 mg of dexamethasone at midnight. RESULTS: Twenty-five patients (83 percent) had remissions during a median follow-up of 42 months (range, 18 to 114). The remissions began 6 to 60 months after radiation therapy, but in most cases (22 patients) remission occurred during the first 2 years. None of the 25 patients had a relapse of Cushing's disease after remission was achieved. There was no relation between the response to radiotherapy and sex, age, urinary cortisol excretion before radiotherapy, the interval between surgery and radiotherapy, whether a pituitary adenoma was found by pathological examination, or tumor size. Seventeen patients had a deficiency of growth hormone after radiation therapy, 10 had a deficiency of gonadotropins, 4 had a deficiency of thyrotropin, and 1 had a deficiency of corticotropin. CONCLUSIONS: Pituitary irradiation is an effective and well-tolerated treatment for patients with Cushing's disease in whom transsphenoidal surgery is unsuccessful.

Adolescent↗
PubMed1997

Galectin-3 inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven rat bone marrow cell proliferation and GM-CSF-induced gene transcription.

The expression of galectin-3 (formerly known as IgE-binding protein or Mac-2) in rat bone marrow (BM) was investigated by FACS, immunocytochemical and immunoblot analysis. The functional significance of rat recombinant galectin-3 on mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven proliferation of macrophage progenitors and gene transcription was further examined. Immunocytochemical analysis of in situ BM sections demonstrated galectin-3 in myelopoietic cells and surrounding stroma, whereas erythropoietic and lymphopoietic environments essentially lacked galectin-3 expression. FACS analysis demonstrated that incubation of freshly isolated BMC with lactose, a competing ligand for galectin-3 binding to glycoconjugates, decreased binding of antigalectin antibodies to cells primarily expressing the myeloid antigen recognized by mAb His-54. Similarly, lectin-mediated binding of exogenous galectin-3 to myeloid lineage cells was also demonstrated. Immunoblot analysis of BM eluates demonstrated galectin-3 both in the extracellular matrix and in a lactose elutable form, bound to the surface of BMC. [3H]Thymidine incorporation studies on BMC cultured in the presence of galectin-3 demonstrated suppression of GM-CSF-induced proliferation by galectin-3. In addition, differential display analysis of immediate early gene expression in BMC cultured in the presence of galectin-3 revealed a 76.2% inhibition of GM-CSF-induced gene transcription by galectin-3 assessed by the number of PCR-fragments generated. Our data suggest a role for galectin-3 in the organization of myelopoietic compartments in rat BM and regulation of the action of growth factors on myelopoietic precursor cells.

Animals↗
PubMed1997

Effects of 1 alpha,25-dihydroxyvitamin D3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: role in cell differentiation, activation and phagocytosis.

The effect of calcitriol/1 alpha,25-dihydroxyvitamin D3, alone and in combination with cytokines, on the expression of various antigens (Ag) on human peripheral blood monocytes and U937 cells was studied by flow cytometry. Both constitutive and interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and tumour necrosis factor-alpha (TNF-alpha)-induced human leucocyte antigen (HLA)-DR, HLA-DP and HLA-DQ Ag expression on monocytes was significantly down-regulated by calcitriol, IL-10 and transforming growth factor-beta (TGF-beta). The effects of calcitriol were concentration dependent and reached maximal inhibitory levels after 3-5 days. Modulation of HLA-DR by calcitriol and IFN-gamma at the protein level correlated with the amount of mRNA specific for the HLA-DR alpha-chain, as judged by Northern blot analysis. The basal as well as IL-4, IL-6, IFN-gamma, TNF-alpha and TGF-beta-driven levels of HLA-ABC Ag were significantly diminished by calcitriol. On U937 cells calcitriol markedly induced CD11a and CD11b expression and weakly up-regulated CD11c whereas on monocytes, constitutive CD11a, CD11b and CD11c expression was significantly down-regulated by calcitriol. The expression of CD14 Ag was strongly induced on U937 cells but only modestly on monocytes. Both the basal level of CD71 and IL-4, IFN-gamma or TNF-alpha-driven expression was diminished on calcitriol-treated U937 cells. In addition, calcitriol suppressed the expression of CD71 Ag on monocytes. The ability of monocytes to phagocytize opsonized Escherichia coli was diminished by calcitriol. Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates expression of MHC, CD11b, CD11c, CD14 and CD71 Ag on both monocytes and U937 cells, and impairs the phagocytic property of monocytes.

Antigens, CD↗
PubMed1997

Subclinical Cushing's syndrome due to adrenal myelolipoma.

We describe a patient with an incidental adrenal myelolipoma associated with biochemical evidence of Cushing's syndrome who lacked the physical stigmata of cortisol excess (subclinical Cushing's syndrome). Pathologic examination revealed the presence of adrenocortical cells mixed with myelolipomatous tissue. Although cases of clinically evident Cushing's syndrome due to adrenal myelolipomas have been reported previously, to our knowledge this is the first report associating adrenal myelolipoma and subclinical Cushing's syndrome.

Adrenal Gland Neoplasms↗
PubMed1996

Soybean agglutinin binds a 160-kDa rat macrophage membrane glycoprotein and enhances cell differentiation and activation.

Mature macrophages (M phi) differ from other rat leukocytes by their ability to bind soybean agglutinin (SBA). In this study we identify the SBA-binding structure on rat bone marrow-derived M phi (BMDM phi). Precipitation of iodinated membrane proteins from rat bone marrow cells (BMC) and BMDM phi with SBA revealed a major glycoprotein of Mr 160 kDa on BMDM phi but not on BMC. In addition minor bands migrating at 70 and 26 kDa were seen. Stimulation of BMDM phi with 100 nM SBA induced a decrease in surface density of Thy1.1 (MRC OX7) and His54 and an increase in the expression of MRC OX6 (RT1.B/I-A), MRC OX17 (RT1.D/I-E), MRC OX41 (gp 110/120), MRC OX42 (CD11b/c), Macl (CD11b/CR3) and Mac2 (galectin-3/IgE binding protein) antigen. Expression of other M phi differentiation antigens recognized by mAb MRC OX43 (M phi, endothelial cells) and ED9 (M phi/CD14 like) were not significantly altered. BMDM phi derived from cultures with M phi colony-stimulating factor (M-CSF) and SBA showed increased oxidative burst and phagocytic activity compared to cells cultured with M-CSF alone. Our data suggest that binding of a 160-kDa membrane glycoprotein on M phi by N-acetylgalactosamine-specific lectins stimulates M phi differentiation and activation.

Animals↗
PubMed1996

Petrosal sinus sampling for diagnosis of Cushing's disease: evidence of false negative results.

OBJECTIVE: While inferior petrosal sinus (IPS) sampling correctly diagnoses pituitary-dependent Cushing's syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushing's disease (e.g. a false-negative result). This study evaluates the results of IPS sampling in patients with Cushing's disease, and compares them with both imaging findings and transsphenoidal examination. DESIGN: The results of IPS sampling were retrospectively compared with both imaging findings and transsphenoidal examination. IPS samples were obtained before and 2, 5 and 10 minutes after intravenous administration of 100 micrograms of CRH. PATIENTS: Thirty-two patients with Cushing's disease were evaluated. All subsequently underwent transphenoidal examination of the pituitary gland. MEASUREMENTS: The ratio of the ACTH concentrations at the IPS and in the peripheral blood (IPS:P ratio), and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were calculated. Radiographic evaluation of the pituitary gland was performed with magnetic resonance imaging (MRI, 29 cases) or computed tomography imaging (CT, 3 cases). RESULTS: Transsphenoidal examination of the pituitary gland revealed a microadenoma in 27 cases. Radiological imaging showed a signal compatible with a microadenoma in 22 cases (68.8%), and correctly located the tumour at the side found at surgery in 14 of the 22 cases with positive transsphenoidal findings (MRI 13 cases, CT 1 case, overall 63.6%). Successful bilateral catheterization was accomplished in 30 patients (93.8%). Samples before and after CRH stimulation were drawn in 24 cases. No major complications were observed with the technique. IPS catheterization correctly predicted Cushing's disease (by means of a significant IPS: P ACTH ratio) in 27 of the 30 patients (90%) with basal sampling, and in 23 of the 24 cases with samples drawn before and after CRH administration (95.8%). Taking into account the 12 patients with a lateral microadenoma shown at transsphenoidal examination, IP sinus ACTH ratio was in agreement with the side recorded by the neurosurgeon in 8/12 cases (66.7%). MRI correctly located the tumour in 8/12 patients (66.7%). One patient showed no significant IPS: P ACTH ratio in any set of samples. His MRI showed no sign of a microadenoma. Two years later, another pituitary MRI evaluation showed a midline hypodense signal. The transsphenoidal examination revealed a microadenoma and the post-operative plasma cortisol and urinary free cortisol fell to 293 nmol/l and 100 nmol/24 h, respectively. CONCLUSIONS: Only when a significant IPS:P ACTH ratio is present can Cushing's disease be established by IPS sampling. The absence of a significant IPS: P ACTH ratio does not necessarily imply ectopic secretion of ACTH, nor does it exclude Cushing's disease. The results of lateralization by IPS sampling do not remove the need for a thorough transsphenoidal examination of the contents of the sella turcica.

Adenoma↗
PubMed1995

Hypothalamic-pituitary dysfunction in patients with craniopharyngioma.

OBJECTIVE: Previous studies of preoperative pituitary function in patients with craniopharyngioma have been limited in scope and have focused on children. We have evaluated the impact of craniopharyngiomas and their surgical treatment on pituitary function in a large group of mostly adult patients. DESIGN: We performed a retrospective study of patients treated at our centre between 1980 and 1992. PATIENTS: Twenty-two men and 13 women, most of them adults, treated surgically for craniopharyngioma during the above period. MEASUREMENTS: Serum glucose, GH, LH, FSH, TSH and cortisol were measured both before and after a combined insulin induced hypoglycaemia, GnRH and TRH test. Basal concentrations of thyroid hormones, PRL and gonadal steroids were also measured. Preoperative computed tomographic scan was performed in all patients, and a detailed study of visual function before and after surgery was available for 32 of them. Endocrine function was reevaluated post-operatively. RESULTS: In preoperative studies, 29 patients had some anterior pituitary deficit and 13 had diabetes insipidus. The most common abnormality was gonadotrophin deficiency, followed by GH deficiency. Dynamic studies suggested a hypothalamic origin for these deficits. In post-surgical evaluation, impaired pituitary function was observed in most patients. Panhypopituitarism was present in 28 cases and diabetes insipidus in 24. CONCLUSIONS: Our report illustrates the high incidence of endocrine deficits in patients with craniopharyngioma. Additional hypothalamic-pituitary dysfunction usually occurs following surgical treatment of these tumours.

Adolescent↗
PubMed1995

Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease.

We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 +/- 15.9%), while in 32 euthyroid patients under antithyroid drug therapy. NK activity was similar to that of controls (46.9 +/- 17.3 and 49.9 +/- 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 +/- 17.9 to 48.1 +/- 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56+ and CD16+ cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 +/- 12.8 to 49.9 +/- 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Usefulness of thyrotropin-releasing hormone test, SMS 201-995, and bromocriptine in the diagnosis and treatment of gonadotropin-secreting pituitary adenomas.

Five patients with gonadotropin-secreting pituitary adenomas were studied. The utility of gonadotropin response to TRH stimulation in the diagnosis and follow-up of these tumors was evaluated, as well as the effects of somatostatin analogue SMS 201-995 and bromocriptine on gonadotropin release. Three patients had FSH and LH secreting adenomas while the other two tumors secreted FSH and alpha-subunit. Transsphenoidal resection of the pituitary adenomas were performed in all patients. Following preoperative TRH administration (400 micrograms i.v.), marked increases were observed in FSH levels in two cases, in LH levels in three and in alpha-subunit in one. The FSH and LH responses to t.his stimulus persisted in the same patients after surgery. Following acute bromocriptine administration (5 mg orally), FSH was reduced in all cases by 19% to 46%, LH in three cases by 50-67% and alpha-subunit in one by 33%. In patient no. 5, with persistent high FSH levels in the immediate postoperative period, long-term bromocriptine treatment was administered (15 mg/d orally), resulting in normalization of FSH levels 6 months later, although the size of the tumor was not reduced. After acute SMS 201-995 administration (100 micrograms sc) FSH decreased in two cases by 38% and 76%, LH in three by 30-56% and alpha-subunit in one by 20%. We conclude that gonadotropin response to TRH stimulation is useful in the diagnosis and follow-up of patients with gonadotroph adenoma. Bromocriptine and SMS 201-995 may be effective as coadjuvant treatment following surgery and radiotherapy in these patients, although long-term studies will be necessary to confirm these proposals.

Adenoma↗