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Results for “TYROSINE DECARBOXYLASE”

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At least 1,603 records · Page 89Linked to original sources
PubMed2001

Effect of alpha-difluoromethyl-ornithine on the expression and function of the epidermal growth factor receptor in human breast epithelial cells in culture.

We have previously shown that ornithine decarboxylase (ODC) overexpression enhances the transforming effects of HER-2neu and epidermal growth factor (EGF) in normal MCF-10A human breast epithelial cells. Our data suggest that such potentiation may be mediated by activation of the mitogen-activated protein kinase (MAPK) pathway and, possibly, STAT signalling. To further explore the interaction between the polyamine pathway and EGF/HER-2neu signalling in this system, we inhibited endogenous ODC activity with alpha-difluoromethylornithine (DFMO) and assessed the effects of this blockade on the expression of EGF receptors (EGFR) and HER-2neu as well as activation of downstream EGF target genes. We found that DFMO administration to MCF-10A cells increased EGF-R mRNA and protein levels in a dose-response fashion, while HER-2neu expression was not affected. The effect of DFMO was mediated through polyamine depletion since it could be reversed by exogenous putrescine administration. Our results also indicated that the increase in EGFR induced by DFMO was not a non-specific consequence of inhibition of cell proliferation. The upregulated EGFRs were functional since they could be phosphorylated by EGF and they were able to promote phosphorylation of downstream signalling molecules including ERK, STAT-3, and STAT-5. We propose that physiologic levels of ODC activity may be critical for regulation of a yet undefined signalling pathway, whose blockade by DFMO leads to a compensatory increase in functional EGFR.

Antineoplastic Agents↗
PubMed2003

Islet autoantibodies in cord blood from patients who developed type 1 diabetes mellitus at 15-30 years of age.

Islet cell autoantibodies are early markers for type 1 diabetes. The aim of this study was to determine whether islet autoantibodies were present at birth in young adults who developed type 1 diabetes at 15-30 years of age. Cord blood sera from 30 patients who developed type 1 diabetes between 15 and 25 years of age and sera from 320 randomly selected control children were tested for islet cell antibodies (ICA) by indirect immunofluorescence and autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GADA), islet cell antigen-2 (IA-2A) and insulin (IAA) by radiobinding assays. The young adults who developed type 1 diabetes did not differ from controls in the cord blood prevalence of any of the four islet autoantibodies. This is in contrast to our previous findings that children who developed type 1 diabetes below 15 years of age had an increased prevalence of cord blood islet autoantibodies. Our present data suggest that, in contrast to children, pre- and perinatal risk factors are less likely to be involved in the development of type 1 diabetes in young adults.

Adolescent↗
PubMed1994

A hepatic tumor associated with bilateral renal angiomyolipomas: a variant of angiomyolipoma?

Angiomyolipoma is usually derived from the kidney and composed of well developed vessels, smooth muscle and fat tissue. The liver is the only extra-renal site of angiomyolipoma. A peculiar type of hepatic tumor accompanied by bilateral renal angiomyolipomas is reported here. The tumor was mostly composed of large epithelioid cells and a small part of hyalinized large vessels and foam cell infiltration. Mature adipose tissue was absolutely absent. Epithelioid tumor cells arranged in an alveolar pattern had abundant glycogen and some diastase-resistant periodic acid-Schiff granules without obvious crystals. Immunohistochemical studies revealed that the epithelioid cells were positive for melanoma specific antibody (HMB-45), S-100 protein, aromatic L-amino acid decarboxylase and focally alpha-smooth muscle actin. Many melanosome- or premelanosome-like, electron-dense granules were observed in these cells. Thus, these cells were characterized by differentiation to both immature melanocytes and smooth muscle cells. These epithelioid cells were similar to some cells in the renal angiomyolipomas of the same patient. The hepatic tumor was considered to be a result of monotonous proliferation of the epithelioid cells seen in renal angiomyolipoma. Differential diagnosis of this tumor was discussed.

Actins↗
PubMed1985

Silver-intensified gold and peroxidase as dual ultrastructural immunolabels for pre- and postsynaptic neurotransmitters.

An ultrastructural immunostaining method that uses silver-intensified gold was combined with another procedure that uses biotin peroxidase conjugates to allow simultaneous identification of two neurotransmitter-related antigens in the central nervous system. Tyrosine hydroxylase-immunoreactive neurons labeled with silver-intensified gold could be differentiated at both light and electron microscopic levels from glutamate decarboxylase-immunoreactive neurons labeled with peroxidase. Cross reactivity of the second group of immunoreagents with the first group was reduced by the heavy metal silver shell formed around the colloidal gold immunoglobulin complex. With this dual pre-embedding method, peroxidase-stained axons containing the inhibitory neurotransmitter gamma-aminobutyric acid were found to synapse directly on silver-stained dopamine neurons in the rat dorsomedial hypothalamus. This approach can be used in combination with a post-embedding immunocytochemical colloidal gold procedure, allowing ultrastructural identification of three neurotransmitter-related antigens in the same tissue section.

Animals↗
PubMed1985

Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor.

Some neurodegenerative disorders may be caused by abnormal synthesis or utilization of trophic molecules required to support neuronal survival. A test of this hypothesis requires that trophic agents specific for the affected neurons be identified. Cholinergic neurons in the corpus striatum of neonatal rats were found to respond to intracerebroventricular administration of nerve growth factor with prominent, dose-dependent, selective increases in choline acetyltransferase activity. Cholinergic neurons in the basal forebrain also respond to nerve growth factor in this way. These actions of nerve growth factor may indicate its involvement in the normal function of forebrain cholinergic neurons as well as in neurodegenerative disorders involving such cells.

Acetylcholine↗
PubMed1986

Possible destruction of cholinoceptive neurons by overstimulation of cholinergic tracts.

It is well established that intracerebral injections of kainic acid may cause not only neuronal cell destruction at the injection site, but also losses in some distant regions. The mechanisms are different. The distant, but not the local, destruction can be produced by folic as well as by kainic acid and prevented by pretreatment of the animal with diazepam. Overexcitation of excitatory projections is believed responsible for the distant damage and evidence is presented that in some instances the projections involved are cholinergic. Thus, for example, injections of kainic acid or folic acid into the substantia innominata of rats destroy neurons in areas such as the pyriform cortex and amygdala which receive cholinergic projections from the injected area. Some of the destroyed neurons are GABAergic. That the distant toxicity in these areas can be partially blocked by scopolamine and is accompanied by decreases in the number of muscarinic binding sites is consistent with a cholinergic mechanism. Distant damage also occurs in the thalamus but this appears to be mediated by a noncholinergic projection. Similar injections of folic acid or kainic acid into the rostral pontine tegmentum, another area with cholinergic cells, cause destruction of both dopaminergic and GABAergic neurons in the substantia nigra. The effect on the GABAergic but not that on the dopaminergic cells is blocked by scopolamine. The results are discussed in relation to possible mechanisms of epilepsy and of selective neuronal losses in diseases such as Parkinson's disease.

Animals↗
PubMed2005

Programmed and induced phenotype of the hippocampal granule cells.

Certain neurons choose the neurotransmitter they use in an activity-dependent manner, and trophic factors are involved in this phenotypic differentiation during development. Developing hippocampal granule cells (GCs) constitutively express the markers of the glutamatergic and GABAergic phenotypes, but when development is completed, the GABAergic phenotype shuts off. With electrophysiological, single-cell reverse transcription-PCR and immunohistological techniques, we show here that short-term (24 h) cultures of fully differentiated adult glutamatergic GCs, which express glutamate, VGlut-1 (vesicular glutamate transporter) mRNA, calbindin, and dynorphin mRNA, can be induced to reexpress the GABAergic markers GABA, GAD67 (glutamate decarboxylase 67 kDa isoform), and VGAT (vesicular GABA transporter) mRNA, by sustained synaptic or direct activation of glutamate receptors and by activation of TrkB (tyrosine receptor kinase B) receptors, with brain-derived neurotrophic factor (BDNF) (30 min). The expression of the GABAergic markers was prevented by the blockade of glutamate receptors and sodium or calcium channels, and by inhibitors of protein kinases and protein synthesis. In hippocampal slices of epileptic rats and in BDNF-treated slices from naive rats, we confirmed the appearance of monosynaptic GABAA receptor-mediated responses to GC stimulation, in the presence of glutamate receptors blockers. Accordingly, GC cultures prepared from these slices showed the coexpression of the glutamatergic and GABAergic markers. Our results demonstrate that the neurotransmitter choice of the GCs, which are unique in terms of their continuing birth and death throughout life, depends on programmed and environmental factors, and this process is neither limited by a critical developmental period nor restricted by their insertion in their natural network.

Animals↗
PubMed1997

Low prevalence of islet autoantibodies in patients with gestational diabetes mellitus.

OBJECTIVE: To determine the proportion of patients with gestational diabetes mellitus (GDM) who have serological characteristics typical of IDDM. RESEARCH DESIGN AND METHODS: Islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD65, and IA-2 antibodies were measured in 145 pregnant women with GDM, 33 with impaired glucose tolerance (IGT), and in 73 with normal glucose tolerance (NGT). ICAs were measured by indirect immunofluorescence; GAD65 and IA-2 antibodies, by a radio-ligand immunoassay incorporating 35S-labeled recombinant antigen; and IAAs, by a liquid-phase radiobinding assay. RESULTS: The prevalences of islet autoantibodies were low and not significantly different between groups. ICAs were detected at levels ranging from 5 to 45 Juvenile Diabetes Foundation U in 14 (10%) women with GDM, 2 (6%) women with (GT, and in 4 (5%) women with NGT. IAAs were detected at levels between 3 and 4 SD above the mean in 4 (3%) women with GDM, 0 women with IGT, and in 1 (1%) woman with NGT. None had both ICAs and IAAs. Neither GAD65 nor IA-2 antibodies, which have been detected in the majority of pre-IDDM and IDDM patients, were found in NGT, IGT, or GDM patients. CONCLUSIONS: Low-titer ICAs and IAAs are not infrequent in pregnant women, but multiple islet autoantibodies and antibodies to GAD65 or IA-2 were not found in GDM. These findings suggest that the serological characteristics of IDDM are rare in GDM.

Adult↗
PubMed1997

The role of late-onset autoimmune diabetes in white familial NIDDM pedigrees.

OBJECTIVE: To determine whether autoimmunity is a prominent feature of NIDDM among diabetic members in families with a strong history of NIDDM or in families with a mixture of NIDDM and IDDM. RESEARCH DESIGN AND METHODS: We determined GAD and islet cell (ICA512) autoantibodies from 215 NIDDM individuals and from 14 individuals with impaired glucose tolerance (IGT) of 68 families, including 1 family with maturity-onset diabetes of the young (MODY) and 3 families ascertained specifically for a mixture of NIDDM and IDDM. We tested 2 control populations: 50 unrelated spouses form Utah families, including 29 spouses with either IGT or NIDDM and 198 random nondiabetic white individuals from Colorado. RESULTS: We detected either GAD or ICA512 autoantibodies in 11 members of seven families and in one spouse used as a control subject. In two families, two affected individuals showed evidence of autoimmunity, but NIDDM individuals in each of the seven families showed no evidence of autoimmunity. Among the five families with both IDDM and NIDDM individuals (three families ascertained for a mixture and two families ascertained with an incidental IDDM child), antibodies were detected in members of only one family. Antibody-positive individuals were significantly younger at diabetes onset and had low waist-to-hip ratios, but were not more likely to be insulin treated. CONCLUSIONS: Autoimmunity is an important cause of apparent NIDDM, even among families with a strong history of NIDDM. However, autoimmunity among affected family members appeared to be a chance event and not the manifestation of a different genetic cause of diabetes.

Adult↗
PubMed1998

Comparison of GAD and ICA512/IA-2 antibodies at and after the onset of IDDM.

OBJECTIVE: Longitudinal changes in GAD antibody (Ab) and ICA512/IA-2 (ICA512) Ab were examined in relation to age at the onset of diabetes and autoimmunity against the thyroid gland. RESEARCH DESIGN AND METHODS: GADAb, ICA512Ab, and antithyroid autoantibody were examined at onset in 40 juvenile-onset IDDM patients (17 males, 23 females, age at onset 9.4 +/- 4.1 years, range 1.7-20). To assess the changes in antibody levels, 29 patients were followed up with sequential serum samples for up to 5 years. RESULTS: At onset, GADAb, ICA512Ab, and antithyroid autoantibody (thyroglobulinAb or thyroid peroxidaseAb) were found in 70, 58, and 25% of the 40 patients, respectively. Prepubertal patients (n = 21) had a significantly higher prevalence and index of ICA512Ab compared with pubertal patients (n = 19) (76 vs. 37%, P = 0.012, and 2.43 +/- 2.36 vs. 0.66 +/- 1.23, P = 0.011), while GADAb was more prevalent in pubertal patients (57 vs. 84%, P = 0.09). A longitudinal analysis of GADAb and ICA512Ab showed that GADAb levels declined more slowly than those of ICA512Ab (P = 0.008). Patients with continuous extremely high levels of GADAb also had high levels of antithyroid autoantibody. CONCLUSIONS: The measurement of ICA512Ab is useful in prepubertal patients, who often show rapid progression of the disease. The presence of autoimmunity against thyroid gland seems to influence the GADAb level but not the ICA512Ab level.

Adolescent↗