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Biomedical subjects

R Toni

Publications and source records attributed to R Toni.

At least 37 records · Page 2Linked to original sources

Neuropeptide-Y-immunoreactive innervation of thyrotropin-releasing hormone-synthesizing neurons in the rat hypothalamic paraventricular nucleus.

The association of neuropeptide-Y (NPY)-immunoreactive (IR) axon terminals with TRH-synthesizing neurons in the rat hypothalamic paraventricular nucleus (PVN) has been studied. Immunocytochemical single and double labeling studies were performed at both light and electron microscopic levels using antiserum to NPY and, as a marker of TRH-containing neurons, antisera recognizing the N-terminal flanking peptides of the TRH prohormone, prepro-TRH-(25-50) and prepro-TRH-(53-74). At the light microscopic level, a diffuse group of TRH-IR cell bodies were observed in the anterior parvocellular subdivision of the PVN and became more numerous and densely clustered in the medial and periventricular parvocellular subdivisions. NPY-IR fibers were observed to innervate all subdivisions of the PVN, but were particularly dense in the anterior, medial, and periventricular parvocellular subdivisions of the nucleus, where they appeared to contact TRH-synthesizing perikarya and neuronal processes. At the ultrastructural level, numerous NPY-IR axon terminals containing labeled vesicles were either tightly juxtaposed to TRH-producing neurons or seen to establish both symmetric and asymmetric synaptic contacts with TRH-containing cell bodies and dendrites. Some NPY-IR axon terminals also established synaptic contacts with unlabeled PVN perikarya and processes or were found in close apposition to blood vessels. These data provide a morphological basis to suggest NPY-mediated neuroendocrine regulation over the biosynthesis and/or secretion of TRH in the PVN. Reports of the colocalization of NPY and catecholamines in the same axon terminals raises the possibility of a potential interaction between NPY and catecholamines to influence TRH neurons in the PVN. Morphological evidence for synaptic interactions between NPY-IR axon terminals and non-TRH-containing neurons in the PVN further suggests that this peptide may influence other neuroendocrine systems.

Animals↗

Intrinsic pituitary interleukin-1 beta is induced by bacterial lipopolysaccharide.

Using a specific antiserum recognizing recombinant rat interleukin-1 beta (IL-1 beta), immunoreactive material was localized to cytoplasmic granules in anterior pituitary endocrine cells and colocalized with TSH in thyrotropes. Authenticity was established by Northern blot hybridization using a specific rat IL-1 beta cRNA probe, revealing a 1.8-kilobase mRNA identical to that in the spleen. The marked increase in anterior pituitary IL-1 beta message after the administration of bacterial lipopolysaccharide, raises the possibility that IL-1 beta may be involved in paracrine or autocrine regulation of pituitary function during infectious challenge.

Animals↗

Isolated adrenocorticotropin deficiency associated with an autoantibody to a corticotroph antigen that is not adrenocorticotropin or other proopiomelanocortin-derived peptides.

A 44-yr-old man with hypocortisolism was shown to have an undetectable basal plasma ACTH level and absent or subnormal ACTH and beta-lipotropin responses to provocative testing with insulin, vasopressin, and CRH. Endocrine function after glucocorticoid replacement was otherwise normal, thus establishing the diagnosis of isolated ACTH deficiency. This patient's serum was tested immunohistochemically for the presence of an antipituitary antibody by indirect immunofluorescence of rat pituitary tissue. Positive immunostaining was observed in stellate-shaped cells in the anterior and intermediate lobes. Immunopositive cells were shown by immunoelectron microscopy to have ultrastructural characteristics of corticotrophs. Immunoreactivity was concentrated in secretory granules 120-170 nm in diameter. In a double immunolabeling procedure, staining by the patient's serum was shown to colocalize with rabbit antiserum to ACTH, but not with antisera to PRL, GH, beta TSH, or beta LH. Immunoabsorption of the patient's serum with ACTH-(1-24), ACTH-(1-39), gamma MSH, corticotropin-like intermediate lobe peptide, beta-endorphin, or beta-lipotropin failed to diminish immunolabeling in the pituitary. We conclude that the antipituitary antibody in this patient's serum shows immunohistochemical specificity for a rat corticotroph antigen located in secretory granules that is neither ACTH nor any of the proopiomelanocortin (POMC)-derived peptides tested. The autoantigen could be a cell-specific granular factor involved in the posttranslational processing of POMC or secretion of ACTH. We postulate that an autoimmune process may account for this patient's disease, and that his antipituitary antibody could play a pathogenic role by either inhibiting a POMC-processing enzyme or initiating an antibody-dependent cell-mediated cytotoxicity reaction, resulting in the selective destruction of corticotrophs.

Adrenocorticotropic Hormone↗

Quantitative clinical anatomy of the pancreatic arteries studied by selective celiac angiography.

The angiographic visualization of the pancreatic arteries, their numerical variations, origins, course and anastomoses, as well as their mean diameter by age-group (20-40, 41-60, greater than 60 years) have been quantitatively investigated by selective celiac angiography in 72 patients without pancreatic disease. Visualization of the various arteries was achieved in a high percentage of cases except for the inferior pancreaticoduodenal arches, due to undervaluation of this vessel by celiac angiography. Confirmation of the great variability of the origin and anastomoses of the dorsal and transverse pancreatic arteries was obtained and possible embryologic reasons and clinical implications of this fact are discussed. Furthermore, a high percentage of multiple (quadruple or more) pancreatica magna and caudae pancreatis arteries has been observed and a functional role of this peculiar arrangement is suggested. Finally, no statistically significant differences were found in the diameter of any artery due to increasing age, probably reflecting maintained neural perivascular control of the pancreatic vessels in the elderly. Satisfactory sensitivity of the angiographic method has been found with respect to the evaluation of visualization and anastomoses of the pancreatic arteries in vivo.

Adult↗

Clinical anatomy of the suprarenal arteries: a quantitative approach by aortography.

The angiographic visualization, arterial origin and mean diameter per age group (20-40, 41-60 years) of the suprarenal arterial vessels have been quantitatively investigated by aortography in 100 patients without suprarenal disease. Visualization of the various arteries was achieved in a percentage substantially comparable to the anatomic data of the literature, though with lower detection of the superior suprarenal vessels. A variable site of origin was present particularly for the superior and middle suprarenal vessels compared to the inferior suprarenal arteries and possible embryological reasons and clinical implications are discussed. Statistically significant differences were found in the mean diameter of each arterial vessel in all the subjects examined, thus substantiating the concept of differential arterial supply to various portions of the gland. Age-related changes were demonstrated in the right middle suprarenal artery, suggesting a predominant role of this vessel in the physiological adaptation of the blood supply to the gland with increasing age.

Adrenal Glands↗

Characterization of human pathological papillary muscles by 1H-NMR spectroscopic and histologic analysis.

Two groups of human pathological papillary muscle samples were analyzed by 1H-NMR spectroscopy and histology. The first group, mainly characterized by hypertrophy of the myocardial cells, interstitial edema and intracellular lipoperoxide accumulation showed similar T1 as well as T2 values. The second group, mainly characterized by hypertrophy of the myocardial cells, fibrosis and areas of necrosis showed T1 values longer than those of the first group while no appreciable differences were evident in the T2 values. These results suggest that a certain degree of correlation exists between the histologic features of the cardiac tissue examined and the relaxation behavior as defined by nuclear magnetic resonance spectroscopy even if a definite association between them is still not possible.

Cardiomyopathies↗

Interdigestive plasma motilin concentrations in aged adults.

The interdigestive plasma motilin concentrations were evaluated in 13 over-65 healthy adults with no evidence of significant disease and in 19 younger individuals. Plasma motilin levels were determined every 15 min during a 3-hr fasting period, using a radioimmunological method. The individual median values of plasma motilin concentrations during the entire study period were significantly higher in aged than younger adults. The individual median coefficients of variation of motilin concentrations and the percentage increases of plasma motilin above baseline at each peak were significantly lower in the aged than in the young group. The results of this study indicate that during the interdigestive period aged individuals have markedly elevated circulating motilin levels, with less pronounced fluctuations than younger persons. This particular hormone pattern could be involved in motor disturbances of the stomach in elderly adults.

Adolescent↗

Adriamycin as a probe for the transversal distribution of cardiolipin in the inner mitochondrial membrane.

The ability of adriamycin to complex cardiolipin was used to determine the distribution of cardiolipin across the inner membrane of rat liver and heart mitochondria. In both mitochondrial types, about 57 +/- 5% of the total cardiolipin was found to be located in the cytoplasmic face of the inner membrane. Mitochondria and mitoplasts were used to study the cytoplasmic face of the inner membrane, purified submitochondrial vesicles with inverted membrane orientation for the matrix face. The cardiolipin amount titrated by adriamycin in the latter was found to be complementary to the amount titrated in the cytoplasmic face. The adriamycin association constant determined for the first saturation level of mitochondria was in good agreement with the value published by Goormaghtigh et al. (Goormaghtigh, E., Chatelain, P., Caspers, J., and Ruysschaert, J. M. (1980) Biochim. Biophys. Acta 597, 1-14) for cardiolipin in artificial membranes. Two binding plateaus were observed when increasing amounts of adriamycin were added to mitochondria. The plateau at higher concentrations is conveniently explained by the penetration of adriamycin into mitochondria and the titration of cardiolipin in the matrix face. Scatchard plot analysis of the binding curves leading to the two plateaus produced almost identical association constants. The total amount of cardiolipin in mitochondria calculated from curves of this type corresponded to the total amount of cardiolipin determined by phosphate analysis of extracts, analyzed by thin layer chromatography.

Animals↗

Cholecystokinin neuron systems and their interactions with the presynaptic features of the dopamine neuron systems. A morphometric and neurochemical analysis involving studies on the action of cholecystokinin-8 and cholecystokinin-58.

A unique role for CCK-58 compared to that for CCK-8 has been demonstrated in the modulation of central catecholaminergic mechanisms and neuroendocrine functions. It is of paramount importance to localize CCK-58 immunoreactivity within the brain in order to establish if separate CCK-58- and CCK-8-immunoreactive neuron systems exist. The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium.

Animals↗

Measurement of immunoreactive gastrin in tissue.

A method for measurement of gastrin in human antral mucosa or in extragastric tissue has been developed and validated. Tissue gastrin was extracted by boiling followed by homogenization at neutral pH. Extractable gastrin immunoreactivity was measured by radioimmunoassay using an antiserum with equal affinity towards G-17 I, G-17 II, G-34 I and G-34 II molecular forms. Almost all extractable gastrin immunoreactivity was recovered after a single extraction and no significant interference by other peptides and/or substances present in tissue was found. The mean gastrin concentration in antral mucosa of healthy subjects was similar to that observed in duodenal ulcer patients, while patients with type A chronic atrophic gastritis or with antral gastrin cell hyperplasia had mean values significantly higher. Gastrin concentration in all specimens from gastrinoma or its metastases was above the upper limit of the range of control tissue. Measurement of tissue gastrin seems to be a valuable tool in the diagnosis of antral gastrin cell hyperplasia and Zollinger-Ellison syndrome.

Adolescent↗

Radioimmunoassay of secretin in human serum.

A sensitive radioimmunoassay for secretin has been developed. Antisera were raised against synthetic porcine secretin coupled to bovine serum albumin. N-alpha- desaminotyrosyl -beta-alanyl secretin was radioiodinated by a slight modification of the chloramine-T method. Pure synthetic porcine secretin was used as a standard. Free and bound hormone were separated by dextran-coated charcoal. No cross-reactivity was found with structurally and physiologically related peptides. The sensitivity of the assay was high enough to measure fasting secretin levels in human serum. Patients with acute or chronic pancreatitis had mean serum secretin concentration not significantly different from healthy subjects. In patients with pancreatic carcinoma the mean serum secretin concentration was significantly lower than in healthy subjects, although a wide overlap of the two groups was evident.

Adolescent↗

Effect of oxygen radicals on heart mitochondrial function in alpha-tocopherol deficient rabbits.

The mitochondria extracted from hearts of alpha-tocopherol deficient rabbits showed a decreased mitochondrial function and an increased formation of oxygen radicals associated with a decreased superoxide dismutase activity. The exposure of the alpha-tocopherol deficient mitochondria to exogeneous oxygen radicals caused a marked decrease in the mitochondrial function with respect to control mitochondria, which was partially reversed by the addition in vitro of alpha-tocopherol.

Animals↗

Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes.

AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice.

AKR murine leukemia virus↗