Biomedical subjects

M Costa

Publications and source records attributed to M Costa.

At least 217 records · Page 12Linked to original sources

PubMed1996

Characterization of excitatory and inhibitory motor neurons to the guinea pig lower esophageal sphincter.

BACKGROUND & AIMS: The lower esophageal sphincter is innervated primarily by enteric motor neurons. The somata of excitatory and inhibitory motor neurons were identified and mapped. METHODS: Retrograde labeling in organotypic culture and immunohistochemistry were used to identify motor neuron somata. RESULTS: 1,1'-Didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (Dil) on the left side of the sphincter labeled descending motor neurons located up to 26 mm along the esophagus and locally (within 2 mm) and gastric motor neurons. Dil applied to the right side of the sphincter labeled descending and local motor neurons but very few gastric motor neurons. Inhibitory motor neuron cell bodies, identified by nitric oxide synthase immunoreactivity, accounted for 86% +/- 4% (n = 6) of descending motor neurons and 53% +/- 4% of local motor neurons labeled from the right side. Excitatory motor neurons, immunoreactive for choline acetyltransferase, accounted for 20% +/- 3% (n = 6) of descending motor neurons and for 47% +/- 4% of local motor neurons. All motor neurons were unipolar, but inhibitory motor neurons were significantly larger than excitatory neurons. CONCLUSIONS: The lower esophageal sphincter is innervated by local excitatory and inhibitory motor neurons and by descending esophageal inhibitory neurons. The oblique muscle, supplied by gastric motor neurons, is closely associated with the gastroesophageal junction.

Animals↗

PubMed1996

Distribution of peptide-containing nerve fibres in achalasia of the oesophagus.

In this study the innervation of the normal human oesophagus was compared with samples taken from 12 patients undergoing Heller's cardiomyotomy for achalasia. The distribution of all nerve fibres in the oesophageal wall was revealed by immunoreactivity to neuron specific enolase and subpopulations of nerve fibres were revealed by immunoreactivity to vasoactive intestinal peptide, neuropeptide Y, enkephalin and substance P. In healthy oesophagus, many nerve fibres immunoreactive for vasoactive intestinal peptide and neuropeptide Y were present in the circular and longitudinal muscle layers of the oesophageal wall and in the cardia of the stomach, whereas fibres immunoreactive for enkephalin and substance P were uncommon. Neuropeptide Y-reactive fibres were commonly seen around blood vessels. In the myenteric plexus cell bodies reactive for vasoactive intestinal peptide and neuropeptide Y were prevalent, as were varicose and non-varicose fibres. In contrast, samples from patients with achalasia revealed few nerve fibres immunoreactive for vasoactive intestinal peptide or neuropeptide Y in either circular or longitudinal muscle, suggesting damage to the inhibitory motor neurons to the muscle layers. Very few fibres were found that were reactive for neuron-specific enolase, indicating that other fibre population (e.g. excitatory cholinergic motor neurons) are also damaged in achalasia. These abnormalities were observed in biopsies from both the constricted and dilated portions of the oesophagus, but the pattern of innervation in the gastric cardia was normal. Myenteric ganglion cells were seen in the oesophagus in only two patients and varicose nerve fibres in the myenteric plexus were uncommon. Neuropeptide Y-reactive perivascular nerve fibres were still found in achalasia as well as non-varicose nerve fibres in the myenteric plexus. These findings indicate damage to all intrinsic neurons in the oesophageal wall in achalasia; however, extrinsic nerve fibres appear to be intact.

Adult↗

PubMed1996

Regeneration of nerve fibres across a colonic anastomosis in the guinea-pig.

Resection and re-anastomosis of the bowel interrupts enteric neuronal pathways. The reestablishment of neuronal connections across a colonic anastomosis was studied using immunohistochemical, retrograde tracing and physiological techniques. In control guinea-pig proximal colon, retrograde labelling with 1,1'-didodecyl-3,3,3,3'-tetramethylindocarbocyanine perchlorate (DiI) revealed that enteric neurons with anally-directed projections are more numerous and have longer axons than orally-projecting neurons. In resected bowel, up to 26 weeks after re-anastomosis, descending neuronal pathways were substantially interrupted. Immunohistochemical labelling of nerve fibres revealed that some enteric nerve fibres did regenerate across narrow regions of the anastomosis, growing preferentially in the oral to anal direction. However, nerve fibres immunoreactive for neurofilament protein triplet were substantially depleted in myenteric ganglia anal to the anastomosis, even after the longest recovery periods, demonstrating that axonal regrowth was limited. This was confirmed in retrograde tracing studies, as no nerve cell bodies oral to an anastomosis were labelled when DiI was placed on myenteric ganglia just anal to the anastomosis. Physiological studies confirmed that regrowth of nerve fibres across the anastomosis occurred and that it was asymmetric, as electrical stimulation led to aboral conduction across the anastomosis more reliably than oral conduction, as measured by circular muscle contraction. After resection and re-anastomosis of the colon, the disruption of neuronal pathways in the enteric nervous system was observed, with limited and preferential re-establishment of aborally-directed long connections.

Anastomosis, Surgical↗

PubMed1996

Probabilistic interpretation of feedforward network outputs, with relationships to statistical prediction of ordinal quantities.

Several problems require the estimation of discrete random variables whose values can be put in a one-to-one ordered correspondence with a finite subset of the natural numbers. This happens whenever quantities are involved that represent integer items, or have been quantized on a fixed number of levels, or correspond to "graded" linguistic values. Here we propose a correct probabilistic approach to such kind of problems that fully exploits all the available prior knowledge about their own structure. In spite of the very stringent constraints induced in output space, the method can be directly applied to standard feed-forward networks while keeping local computation of both outputs and error signals. According to these guidelines, we devised a neural implementation of a complex image pre-processing algorithm by using very poor resolution on the computing elements in the network.

Algorithms↗

PubMed1996

Monitoring human lymphocytic DNA-protein cross-links as biomarkers of biologically active doses of chromate.

A simple and sensitive assay for DNA-protein cross-links has been used as a biomarker of chromate exposure and early carcinogenic effects. Pilot studies of DNA-protein cross-links in peripheral blood lymphocytes have been conducted with individuals who had higher exposure to chromate, including welders, and with individuals who had lower levels of exposure such as residents living in a chromium-contaminated area in Jersey City, New Jersey. Studies were also conducted in two Bulgarian cities (Jambol and Burgas) with different levels of air pollution and Cr(VI) exposure and in chrome platers in Bulgaria who had high exposure to chromate. DNA-protein cross-links in U.S. welders and in individuals living in Hudson County, New Jersey around chromium-contaminated areas were significantly higher compared to matched controls. Although blood and urinary levels of chromium were not extensively studied in these populations, we were able to obtain these measurements in the Bulgarian population. Chromium levels in red blood cells of controls living in Burgas were in the order of 1 to 2 ppb chromium, and these individuals had the lowest levels of DNA-protein cross-links. However, the chromium levels in Jambol ranged from about 2 to 7 ppb in red blood cells of city residents to about 22 ppb in chrome platers. DNA-protein cross-links were saturated at about 7 to 8 ppb chromium in the red blood cells, and cross-links correlated well only with chromium levels in red blood cells. Urinary chromium levels did not correlate well with either DNA-protein cross-links or chromium levels in with red blood cells.

Biomarkers↗

PubMed1996

[Intermittent prophylaxis in febrile seizures with oral diazepam: study of 82 cases].

We present our results of intermittent prophylaxis with oral diazepam in febrile seizures. We treated 82 patients aged between 3 months and 5 years. They have had simple or complex febrile seizures. Recurrence occurred in 22 patients (26%), none had a long-lasting febrile convulsion. Transient side effects occurred in 21.95% of the cases. We conclude that diazepam is a safe and effective drug for prophylaxis of febrile seizures when used as soon as any sign of illness appears. We suggest, however, that the administration of the drug should be indicated if the child presents at least one consistent predictor of risk of recurrent febrile seizures.

Child, Preschool↗

PubMed1996

Expression of transporter associated with antigen processing-1 in the endocrine cells of human pancreatic islets: effect of cytokines and evidence of hyperexpression in IDDM.

A possible role of transporter associated with antigen processing (TAP)-1 in the pathogenesis of IDDM has been investigated by examining the level of TAP-1 expression in the islets of IDDM pancreas and by studying in vitro the effect of interferon (IFN)-gamma, IFN-alpha, and tumor necrosis factor-alpha in TAP-1 expression by cultured islet cells. A remarkable hyperexpression of TAP-1 has been found in the endocrine cells (beta and non-beta) of IDDM islets, which constitutes first evidence of hyperexpression of this molecule in the target organ of an autoimmune disease. TAP-1 hyperexpression correlated clearly with HLA class I hyperexpression but only very partially with HLA class II ectopic expression. IFN-gamma and IFN-alpha, both cytokines putatively implicated in IDDM pathogenesis, were capable of inducing TAP-1 protein (as assessed by immunofluorescence flow cytometry) and message (by Northern blot analysis and reverse transcription polymerase chain reaction). These findings suggest that under the influence of cytokines (most probably IFN-alpha) beta-cells may express in their surface a high density of HLA class I-peptide complexes that may facilitate their recognition and lysis by low-affinity CD8+ T-cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

[The laryngeal mask in pediatric anesthesia].

We carried out a perspective study in order to assess the ease of insertion, the type and the incidence of perioperative complications connected with the use of the Laryngeal Mask Airway (LMA). We examined 300 consecutive patients, M/F 261/39, average age 4.2 yrs. (range 0.1-16), ASA I-II, who underwent surgical operations of short or average length not involving the pleural, the oropharyngeal or the peritoneum cavity. The choice about anesthesia was left to the discretion of the anesthesiologist. In 27 cases the position of the LM was controlled through a flexible fiberoptics. In 269 patients (89.6%) the LMA was correctly positioned during the first attempt. In 27 patients (9%), 2 or more attempts were necessary, and in 4 patients (1.4%) it was not possible to set the LMA. No differences of statistical significance were noticed between the different size of LMA, with regards to the facility of insertion. The control through fiberoptics showed a correct position, from an anatomical point of view, in 11 patients (41%), whereas in 13 patients (48%) some signs of partial obstruction were noticed (epiglottis interposing between the opening of LMA and larynx) and in 3 patients (11%) vocal cords are not visible. The following complications took place: laryngeal spasm on induction (2.3%), cough or movements on positioning (2.3%), hypoxia (4.3%), obstruction (1%), laryngeal spasm on awakening (1.7%), trauma (5%) and vomiting (0.3%). No connections were found between the size of LMA and total complications. Nevertheless, cough or movement during positioning and laryngeal spasm on awakening were significantly more frequent with LMA n. 3. In our experience, the LMA proved to be effectual and safe in the control of the airway during elective operations in pediatric surgery.

Adolescent↗

PubMed1996

The enteric neural network and three dimensional computer modelling of intestinal peristalsis.

A computer model of the enteric nervous system has been developed using MATLAB in order to determine the extent to which the nature of intestinal activity can be explained by our current understanding of the projections and connectivity of enteric neurons. The model is based on repeated, identical overlapping modules, each of which contains the same number of neurones and circular muscle. The connections between modules were derived from microanatomical data. This simple model explains some characteristic features of the generation of an intestinal motor pattern.

Animals↗

PubMed1995

Intra-arterial beta irradiation prevents neointimal hyperplasia in a hypercholesterolemic rabbit restenosis model.

BACKGROUND: Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems. METHODS AND RESULTS: Flexible 90-yttrium (90Y) coils inside a centering balloon were used to allow homogeneous intraarterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245 +/- 93 cells/cm in control, 42 +/- 27 in 6 Gy, 72 +/- 107 in 12 Gy, and 2 +/- 2 in 18 Gy groups; P < .001) and in total neointimal cells (891 +/- 415 cells/cm in control, 79 +/- 43 in 6 Gy, 192 +/- 264 in 12 Gy and 22 +/- 13 in 18 Gy groups; P < .0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26 +/- 10% in the control group to 1 +/- 1.3% in the 18 Gy group (P < .0001), but lower doses had no significant effect. CONCLUSIONS: Administration of intra-arterial beta irradiation with a 90Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.

Angioplasty, Balloon↗

PubMed1995

F-syndrome (F-form of acro-pectoro-vertebral dysplasia): report on a second family.

We report on a father and daughter in the second known family affected with F-syndrome. The first family, with 8 affected members, was reported by Grosse et al. [1969: BD:OAS V (3):48-63]. F-syndrome, an autosomal-dominant trait, is mainly characterized by acral defects that may also involve the sternum and the lumbosacral spine. Synostoses between capitate and hamate, and between talus and navicular, are invariably present; other carpal and tarsal bones are sometimes incorporated into the fusion. The hand malformation is principally a malformation of the first 2 rays. In our patients, the short and malformed thumb was webbed with the index finger, which was radially deviated with duplication of the middle and distal phalanges. In the feet, polydactyly and severe metatarsal and toe anomalies were present. The father had a prominent sternum with pectus excavatum, whereas the daughter had no sternal deformity. Both of them had a mild failure of fusion of posterior arch L5 and/or S1.

Abnormalities, Multiple↗

PubMed1995

Frequent use of the same tertiary motif by self-folding RNAs.

We have identified an 11 nucleotide RNA motif, [CCUAAG...UAUGG], that is extraordinarily abundant in group I and group II self-splicing introns at sites known, or suspected from co-variation analysis, to interact with hairpin terminal loops with a GNRA consensus sequence. Base substitution experiments using a ribozyme-substrate system derived from a group I intron reveal that this motif interacts preferentially with GAAA terminal loops and binds them with remarkable affinity, compared with other known combinations of GNRA loops and matched targets. A copy of the [CCUAAG...UAUGG] motif which is present in domain I of many group II introns is shown to interact with the GAAA terminal loop that caps domain V. This is the first interaction to be identified between these two domains, whose mutual recognition is known to be necessary and sufficient for group II ribozymic activity. We conclude that interaction of [CCUAAG...UAUGG] with GAAA loops is one of the most common solutions used by nature to solve the problem of compacting and bringing together RNA structural domains.

Base Sequence↗

PubMed1995

Synpolydactyly (type II syndactyly) with aplasia/hypoplasia of the middle phalanges of the toes: report on a family with eight affected members in four generations.

We describe a new family with synpolydactyly (syndactyly type II) with 8 affected members in 4 generations. Aplasia/hypoplasia of the middle phalanges of the toes was also noted. In our opinion, this anomaly represents a frequent manifestation of synpolydactyly. No other major skeletal or extraskeletal malformations were present.

Adult↗

PubMed1995

Ultrastructural studies of the myenteric plexus and smooth muscle in organotypic cultures of the guinea-pig small intestine.

External muscle and myenteric plexus from the small intestine of adult guinea-pigs were maintained in vitro for 3 or 6 days. Myenteric neurons and smooth muscle cells from such organotypic cultures were examined at the electron-microscopic level. An intact basal lamina was found around the myenteric ganglia and internodal strands. Neuronal membranes, nuclei and subcellular organelles appeared to be well preserved in cultured tissues and ribosomes were abundant. Dogiel type-II neurons were distinguishable by their elongated electron-dense mitochondria, numerous lysosomes and high densities of ribosomes. Vesiculated nerve profiles contained combinations of differently shaped vesicles. Synaptic membrane specializations were found between vesiculated nerve profiles and nerve processes and cell bodies. The majority of nerve fibres were well preserved in the myenteric ganglia, in internodal strands and in bundles running between circular muscle cells. No detectable changes were found in the ultrastructure of the somata and processes of glial cells. Longitudinal and circular muscle cells from cultured tissue had clearly defined membranes with some close associations with neighbouring muscle cells. Caveolae occurred in rows that ran parallel to the long axis of the muscle cells. These results indicate that the ultrastructural features of enteric neurons and smooth muscle of the guinea-pig small intestine are well preserved in organotypic culture.

Animals↗

PubMed1995

Increased DNA-protein crosslinks in lymphocytes of residents living in chromium-contaminated areas.

It has been known for a number of years that chromium-containing mine slags were used as landfill in residential areas of Hudson County, New Jersey. Since one of the major lesions induced in intact cells by chromate is the DNA-Protein crosslink, we have used this lesion as a biomarker of biological effect of chromium (Cr) exposure. We have previously developed a sensitive and easy-to-perform assay to detect DNA-Protein crosslinks, based on the selective K SDS precipitation of DNA associated with protein. We examined the levels of DNA-Protein crosslinks in peripheral blood mononuclear cells of 33 individuals determined to be at risk for chromium exposure by virtue of their residence in Hudson County and their urinary Cr levels. These data were compared to the levels of DNA-Protein crosslinks among 49 controls who resided in noncontaminated areas. A complete clinical examination and urine analysis did not show any Cr-related abnormalities among the exposed population. The mean DNA-Protein crosslink level in the lymphocytes of the exposed group was 1.3 +/- 0.5% (SD), whereas the unexposed group had 0.8 +/- 0.4% (p < 0.001), after adjustment for age, gender, race, smoking, and weight. Further studies in this population are needed to confirm the possible association between the high levels of DNA-Protein crosslink and Cr exposure.

Adult↗

PubMed1995

The morphology and projections of retrogradely labeled myenteric neurons in the human intestine.

BACKGROUND & AIMS: Myenteric ganglia in the human gastrointestinal tract contain a mixture of many different types of nerve cells that cannot be distinguished by their location. The aim of this study was to characterize different functional types of cells by using retrograde labeling in vitro to identify neurons according to their targets. METHODS: The retrograde label 1,1'-didodecyl 3,3,3',3'-indocarbocyanine perchlorate (Dil) was applied to different target layers of human small or large intestine. After 3-5 days in organotypic culture, myenteric neurons projecting to the Dil application site were visualized and mapped using fluorescence microscopy. RESULTS: Myenteric motor neurons projecting to the external muscle layer were typically unipolar cells with lamellar dendrites (Dogiel type I) and had short projections up to 16 mm long. In contrast, presumed interneurons with Dogiel type I morphology were shown to project up to 68 mm aborally or up to 38 mm orally. Multipolar Dogiel type II neurons with smooth cell bodies were labeled most frequently from the submucous plexus. No myenteric neurons were labeled by Dil applied to the mucosa. CONCLUSIONS: Myenteric neurons labeled from each target had characteristic size, morphology, polarity, and length of projections, indicating that there is a high degree of organization in the human enteric nervous system.

Aged↗

PubMed1995

Model for the epigenetic mechanism of action of nongenotoxic carcinogens.

On the basis of studies with carcinogenic nickel compounds, we propose a new model of how epigenetic carcinogens might act. This model is based on the fact that nickel compounds induce an increase in chromatin condensation, causing neighboring genes that are actively expressed in euchromatin to be condensed into heterochromatin. Such redistribution in condensation of chromatin would probably only be transient were it not for the DNA cytosine methyl transferase enzyme, which through de novo methylation can cause genes to be inherited in an active state. Actively expressed genes have less cytosine methylation in their promoter whereas hypermethylation of cytosine in promoters is characteristic of inactive genes. Therefore, nickel, through induction of an enhanced condensation state of chromatin that results in the incorporation of critical genes such as the senescence and tumor suppressor genes into heterochromatin (ie, thread on a spool) and the subsequent methylation of this DNA, silences the genetic activity that might be essential for maintenance of a normal cell. This model is consistent with the literature on cytosine methylation and is also consistent with studies of nickel carcinogenesis showing that it increases cytosine methylation. It is also consistent with nickel carcinogenesis being synergistic with many other mutagenic carcinogens (ie, x rays, benzopyrene, or ultraviolet light), which has always suggested that it has a unique component that is not part of the mechanism of these mutagenic carcinogens.

Animals↗

PubMed1995

Glutathione and free amino acids form stable complexes with DNA following exposure of intact mammalian cells to chromate.

Exposure of cells to carcinogenic Cr(VI) compounds results in the formation of several types of DNA lesions such as strand breaks, DNA-protein crosslinks and uncharacterized DNA-Cr adducts. Hexavalent chromium compounds are positive in most bacterial and eukaryotic mutagenic systems, although the nature of DNA modifications underlying the chromium-induced mutagenesis is not known. Hexavalent chromate(VI) is very active in cellular systems because it is actively transported into cells, but intracellularly it is ultimately reduced to Cr(III). Here we show that exposure of Chinese hamster ovary (CHO) cells to potassium chromate(VI) leads to the formation of stable complexes between DNA and amino acids or glutathione. Cysteine, glutamic acid and histidine were the major amino acids crosslinked to DNA in chromate-treated cells. Incubation of purified DNA in the presence of EDTA dissociated SDS stable amino acid-DNA complexes, which indicates that these DNA adducts are most likely to represent ternary coordination complexes mediated by Cr(III) rather than covalent linkage between amino acids/glutathione and DNA. The amino acids that were found complexed with DNA purified from chromate-exposed cells did not orginate from previously crosslinked proteins during DNA isolation, but represented authentic reactions of free amino acids and glutathione with chromium and DNA in cells. Ternary complexes of glutathione or amino acids with Cr(III) and DNA were estimated to account for as much as 50% of DNA-bound chromium following exposure to < or = 25 microM chromate.

Amino Acids↗