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Biomedical subjects

J Diaz

Publications and source records attributed to J Diaz.

At least 73 records · Page 4Linked to original sources
PubMed1998

Functional implications of multiple dopamine receptor subtypes: the D1/D3 receptor coexistence.

The D3 dopamine receptor, a D2-like receptor, is selectively expressed in the ventral striatum, particularly in the shell of nucleus accumbens and islands of Calleja, where it is found in medium sized substance P neurons. The latter co-express the D1 receptor whose interaction with the D3 receptor was studied by treating rats with selective agonists and antagonists. In agreement with the opposite cAMP response, they mediate in cultured neuroblastoma cells, the D1 and D3 receptors exerted opposite influences on c-fos expression in islands of Calleja. However, in agreement with the synergistic influence of cAMP on D3 receptor-mediated mitogenesis on the same cultured cells, D1 and D3 receptor stimulation in vivo synergistically enhanced preprotachykinin mRNA in the shell of accumbens. This indicates that the two receptor subtypes may affect neurons in either synergy or opposition according to the cell or signal generated. Levodopa-induced behavioral sensitization in hemiparkinsonian rats is another example of D1/D3 receptor interaction. Hence repeated levodopa administration induces the ectopic appearance of the D3 receptor in substance P/dynorphin, striatonigral neurons of the dorsal striatum. This induction is secondary to D1 receptor stimulation in neurons of the denervated side and fully accounts for the sensitization, i.e. the increased behavioral responsiveness to levodopa. During brain development, a similar process could operate to control the late appearance of the D3 receptor in D1-receptor bearing neurons of the ventral striatum at a time at which they start to be innervated by dopamine neurons. Finally, taking into account a variety of genetic, developmental, neuroimaging and pharmacological data, we postulate that imbalances between the levels of D1 and D3 receptors in the same neurons could be responsible for schizophrenic disorders.

Animals↗
PubMed1998

Fibrinogen and fibrinolysis in blood and in the arterial wall: its role in advanced atherosclerotic disease.

High plasma fibrinogen appears to be an important risk factor for the development of atherosclerosis. The aim of our study was to measure fibrinogen and fibrin degradation products (D-dimer), interleukin-6 tissue plasminogen activator, plasminogen activator inhibitor-1 and urokinase-type plasminogen activator in the plasma and arterial walls of 45 patients who had arterial surgery between April 1993 and November 1995. The arterial specimens were also examined by immunohistochemists for these same factors. The serum fibrinogen and fibrin degradation products were high in all patients, and fibrinolysis was depressed. Few leukocytes were seen in the arterial walls, which had poor fibrinolytic activity. Plasminogen-activator inhibitor activity in the wall was also reduced in the affected arterial walls. The abdominal aorta appeared to have the highest levels of fibrinogen and this may be related to its ability to form aneurysms. Fibrinogen may play an important role in the progression of atherosclerotic disease.

Aorta, Abdominal↗
PubMed1998

Weight variation in users of the once-a-month injectable contraceptive Cyclofem.

This study was aimed to evaluate weight variation in 3183 women using the injectable contraceptive Cyclofem. All women were allocated to groups according to their weight at admission. The weight gain was inversely proportional to the weight at admission. The groups of women weighing less than 50 kg at admission, experienced a higher increase, 2.8% in four months, and they continued gaining weight, reaching 7.7% in 13 months. Women weighing more than 64 kg at admission did not present any weight change in 4 months and increased only 1.7% at 13 months. When women were classifed as discontinuers due to weight increase, discontinuers due to other reasons, and continuers, at four months, the differences in the mean weight between the groups was statistically significant only in the groups weighing 55 kg or more at admission. At 13 months, the results were similar and the differences were statistically significant only in the groups weighing 55-59 kg and 60-64 kg. Discontinuation rates due to weight increase were proportional to the weight at admission. This rate was almost three times higher in the group of women weighing more than 64 kg at admission than in the group weighing less than 55 kg (p<0.001). In conclusion, considering the data presented in this study, it is impossible to recommend health providers to inform women who choose Cyclofem as their contraceptive method, that this method may increase their weight throughout its use.

Adult↗
PubMed1998

A rat G protein-coupled receptor selectively expressed in myelin-forming cells.

By screening an olfactory bulb cDNA library using dopamine receptor probes, we isolated the cDNA coding for the rat counterpart of an orphan receptor known as Edg-2, homologous to G protein-coupled receptors. In situ hybridization analysis showed that Edg-2 mRNA expression is restricted to myelinated structures, e.g. corpus callosum or peripheral nerves. A weaker expression in various peripheral organs was also detected in newborns. A 3.8-kb transcript was found at high levels in highly myelinated brain structures and sciatic nerve, and, at lower levels, in poorly myelinated peripheral organs, consistent with its occurrence in Schwann cells in the peripheral nervous system. One hundred percent of Edg-2 mRNA-containing cells in the brain also expressed mRNA encoding myelin-basic-protein, a marker of oligodendrocytes. This restricted olygodendrocytes localization was confirmed by the absence of cellular colocalization of Edg-2 and glial fibrillary acidic protein, an astrocytic marker. During prenatal development, Edg-2 mRNA expression was high in the cortical neuroepithelium and meningeal layer at E16, extended later to other neuroepithelia, and disappeared shortly after birth. During brain postnatal development, Edg-2 mRNA expression in myelinated structures followed a caudo-rostral gradient, similar to that of myelination. Thus, Edg-2 is the first G protein-coupled receptor found to be selectively expressed in myelin-forming cells in the nervous system and its temporal expression pattern is consistent with a dual role (i) in neurogenesis, during embryonic development, and (ii) in myelination and myelin maintenance, during postnatal life.

Animals↗
PubMed1998

Coexpression of dopamine D1 and D3 receptors in islands of Calleja and shell of nucleus accumbens of the rat: opposite and synergistic functional interactions.

Using double in situ hybridization, we found extensive coexpression of dopamine D1 and D3 receptor (D1R and D3R) mRNAs in neurons of the island of Calleja major (ICjM) and ventromedial shell of nucleus accumbens (ShV), respectively. Thus, at least 79 and 63% of D3R mRNA-expressing neurons in ICjM and ShV also expressed the D1R mRNA. Coexpression of D1R and D3R mRNAs was found to occur in substance P (SP) mRNA-expressing neurons in both areas, suggesting SP mRNA as a marker of the activity of coexpressing neurons. Administration of SKF 38393, a D1R receptor agonist, increased c-fos mRNA in ICjM, whereas administration of quinpirole, a D2R/D3R agonist, decreased it; SCH 23390, a D1 R antagonist and nafadotride, a preferential D3R antagonist, given alone, had effects opposite to those of the corresponding agonists. These data indicate that basal c-fos expression in ICjM is maintained by endogenous dopamine acting tonically upon two receptor subtypes subserving opposite effects on the same cell. However, in ShV, whereas SKF 38393 also increased c-fos mRNA, quinpirole had no effect, a difference presumably reflecting the lower fraction of neurons coexpressing D1R and D3R in this area. In contrast, in ShV from reserpine-treated rats, SKF 38393 increased SP mRNA and quinpirole potentiated this effect. These contrasting interactions of D1R- and D3R-mediated signalling events, i.e. in either opposite or synergistic directions, most likely occurring at the single cell level, may serve to increase the dopamine response threshold of the target cells in ICjM and to maintain a strong tonic activity of ShV neurons.

Animals↗
PubMed1998

Pigmented squamous cell carcinoma of the skin: report of two cases and review of the literature.

Melanoma is the most common malignant tumor in which melanin synthesis occurs, although other nonmelanocytic tumors synthesize melanin or contain nonneoplastic melanocytes. We present two cases of infiltrating pigmented squamous cell carcinoma of the skin and review the clinical, morphologic, and ultrastructural features. Melanin was found in epithelial tumor cells as well as in macrophages and dendritic melanocytes. Interestingly, one of the neoplasms was associated with an adjacent melanocytic nevus and pigmented solar keratosis. Immunohistochemical analysis showed that neoplastic cells stained for keratin and melanin-filled dendritic cells were found to be S-100 protein and HMB45 positive. A careless examination of the immunohistochemical stains for S-100 protein and HMB45 could cause the misdiagnosis of melanoma, a neoplasm that has a more ominous outlook.

Aged↗
PubMed1998

[Function and therapeutic potential of the dopamine D3 receptor].

The D3 receptor is recognized with high affinity by all antipsychotics and selectively expressed in limbic brain areas participating in the central of emotions, motivation and reward. In transfected cultured cells, stimulation of the D3 receptor inhibits cAMP formation and increases mitogenesis, which, in turn, is potentiated by activation of the cAMP cascade. This suggests that both opposite and synergistic interactions occur between the D3 receptor and the cydic AMP pathway, possibly underlying D1/D3 receptor interactions. In fact, D1 and D3 receptors colocalize in the islands of Calleja, in which they interact in opposition on c-fos mRNA expression, and in the shell of nucleus accumbens, in which they interact in synergy on substance P mRNA expression. The expression of the D3 receptor is highly dependent of the dopamine innervation: lesion of ascending dopamine neurons reduces D3 receptor mRNA and binding in the shell of nudeus accumbens, by deprivation of an unknown factor of dopamine neurons, distinct form dopamine and its cotransmitters. In agreement, expression of the D3 receptor in neurons during rat brain development starts after the settlement of dopamine innervation during the first postnatal week. However, in adult rats with a unilateral lesion of dopamine neurons, repeated treatment with levodopa rescues D3 receptor expression in the shell of nudeus accumbens and induces this expression in the dorsal striatum, a region controlling movements in which the D3 receptor is normally absent. This induction seems responsible for the behavioral sensitisation, i.e. increased responsiveness to levodopa. These observations suggest a role of the D3 receptor in the progressive increase in the therapeutic efficacy of levodopa in the initial treatment of Parkinson's disease, and/or its adversive motor and psychopathological effects during long-term treatment. Finally, various pharmacological and genetic data suggest a role of the D3 receptor in drug addiction and schizophrenia, the treatment of which could benefit from selective D3R agents.

Animals↗
PubMed1998

Hemangiopericytoma ischiorectal. Report of a case.

Hemangiopericytoma (HP) is a rare tumoral neoplasm of the soft tissues. Here, we report a case of HP that appeared in a young woman in a very uncommon location (perianal). Initially it was considered as a perianal abscess: arteriography, CT-scan and, eventually, histological studies, confirmed the diagnosis of HP. The tumoral mass was first embolized and thereafter was resected through a double approach (abdominal and perineal). One and a half years after surgery, the patient remains asymptomatic.

Adult↗
PubMed1997

Polarized expression of Ca2+ channels in pancreatic and salivary gland cells. Correlation with initiation and propagation of [Ca2+]i waves.

In polarized epithelial cells [Ca2+]i waves are initiated in discrete regions and propagate through the cytosol. The structural basis for these compartmentalized and coordinated events are not well understood. In the present study we used a combination of [Ca2+]i imaging at high temporal resolution, recording of Ca2+-activated Cl- current, and immunolocalization by confocal microscopy to study the correlation between initiation and propagation of [Ca2+]i waves and localization of Ca2+ release channels in pancreatic acini and submandibular acinar and duct cells. In all cells Ca2+ waves are initiated in the luminal pole and propagate through the cell periphery to the basal pole. All three cell types express the three known inositol 1,4,5-trisphosphate receptors (IP3Rs). Expression of IP3Rs was confined to the area just underneath the luminal and lateral membranes, with no detectable receptors in the basal pole or other regions of the cells. In pancreatic acini and SMG ducts IP3R3 was also found in the nuclear envelope. Expression of ryanodine receptor was detected in submandibular salivary gland cells but not pancreatic acini. Accordingly, cyclic ADP ribose was very effective in mobilizing Ca2+ from internal stores of submandibular salivary gland but not pancreatic acinar cells. Measurement of [Ca2+]i and localization of IP3Rs in the same cells suggests that only a small part of IP3Rs participate in the initiation of the Ca2+ wave, whereas most receptors in the cell periphery probably facilitate the propagation of the Ca2+ wave. The combined results together with our previous studies on this subject lead us to conclude that the internal Ca2+ pool is highly compartmentalized and that compartmentalization is achieved in part by polarized expression of Ca2+ channels.

Adenosine Diphosphate Ribose↗
PubMed1997

Polarized expression of Ca2+ pumps in pancreatic and salivary gland cells. Role in initiation and propagation of [Ca2+]i waves.

The present study was aimed at localization of plasma membrane (PMCA) and intracellular (SERCA) Ca2+ pumps and characterizing their role in initiation and propagation of Ca2+ waves. Specific and polarized expression of Ca2+ pumps was observed in all epithelial cells examined. Immunolocalization revealed expression of PMCA in both the basolateral and luminal membranes of all cell types. SERCA2a appeared to be expressed in the luminal pole, whereas SERCA2b was expressed in the basal pole and the nuclear envelope of pancreatic acini. Interestingly, SERCA2b was found in the luminal pole of submandibular salivary gland acinar and duct cells. These cells expressed SERCA3 in the basal pole. To examine the significance of the polarized expression of SERCA and perhaps PMCA pumps in secretory cells, we compared the effect of inhibition of SERCA pumps with thapsigargine and partial Ca2+ release with ionomycin on Ca2+ release evoked by agonists and Ca2+ uptake induced by antagonists. Despite their polarized expression, Ca2+ uptake by SERCA pumps and Ca2+ efflux by PMCA resulted in uniform reduction in [Ca2+]i. Surprisingly, inhibition of the SERCA pumps, but not Ca2+ release by ionomycin, eliminated the distinct initiation sites and propagated Ca2+ waves, leading to a uniform increase in [Ca2+]i. In addition, inhibition of SERCA pumps reduced the rate of Ca2+ release from internal stores. The implication of these findings to rates of Ca2+ diffusion in the cytosol, compartmentalization of Ca2+ signaling complexes, and mechanism of Ca2+ wave propagation are discussed.

Animals↗
PubMed1997

Selective expression of dopamine D3 receptor mRNA in proliferative zones during embryonic development of the rat brain.

We studied by in situ hybridization histochemistry the expression of D3 receptor (D3R) mRNA at various stages of rat brain development. The first expression of D3R mRNA was detected at embryonic day 14 (E14) in the striatal and rhinencephalic neuroepithelia and throughout the tectal neuroepithelium. From E16 to E19 D3R mRNA expression extended along a rostrocaudal axis to additional proliferative ventricular zones of the basal forebrain, including the neuroepithelia of the olfactory bulb, nucleus accumbens, septum, and amygdala, whereas D1 and D2 receptor (D1R and D2R) mRNAs were expressed predominantly by migrating neuroblasts and/or differentiating striatal neurons. Only a few neuroblasts, migrating in the lateral cortical stream or developing as cerebellar Purkinje cells, expressed D3R mRNA from E18. At birth D3R expression mRNA appeared in differentiating neuronal fields of the nucleus accumbens and medial mamillary body primordia and on P5 reached a distribution similar to that found in adult. In addition, a transient upregulation was detected on P5 in the medial mamillary bodies, parietofrontal cortex, and olfactory tubercle. In the adult brain D3R gene expression continued in the striatal proliferative subventricular zone. The late expression D3R mRNA in neurons, after achievement of dopamine innervation, supports the existence of a regulating factor released from dopamine neurons, as suggested by denervation studies in the adult. The sustained and abundant D3R gene expression, predominantly in germinative neuroepithelial zones actively involved in neurogenesis of most basal forebrain structures, supports the hypothesis of a neurogenetic but minor morphogenetic modulatory role for the D3R during CNS development.

Animals↗
PubMed1997

Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa.

In rats with unilateral lesions of the nigrostriatal dopamine pathway with 6-hydroxydopamine, the motor stimulating effects of levodopa, an indirect dopamine receptor agonist, evidenced by contraversive rotations, become enhanced upon repeated intermittent administration. However, the mechanisms of this behavioral sensitization are essentially unknown. We show that development of sensitization is accompanied by a progressive appearance of D3 receptor mRNA and binding sites, visualized by in situ hybridization and 7-[3H] hydroxy-N,N-di-n-propyl-2-aminotetralin autoradiography, respectively, occurring in the denervated caudate putamen, a brain area from which this receptor subtype is normally absent. Development and decay of these two processes occur with closely parallel time courses, whereas there were no marked changes in D1 or D2 receptor mRNAs. D3 receptor induction by levodopa is mediated by repeated D1 receptor stimulation, since it is prevented by the antagonist SCH 33390 and mimicked by the agonist SKF 38393, but not by two D2 receptor agonists. The enhanced behavioral response to levodopa is mediated by the newly synthesized D3 receptor, since it is antagonized by nafadotride, a preferential D3 receptor antagonist, in low dosage, which has no such effect before D3 receptor induction. D3 receptor induction and behavioral sensitization are also accompanied by a sustained enhancement of prodynorphin mRNA level and a progressively decreasing expression of the preprotachykinin gene. We propose that imbalance between dynorphin and substance P release from the same striatonigral motor efferent pathway, related to D3 receptor induction, is responsible for behavioral sensitization.

Animals↗
PubMed1997

One-on-one mentor-resident rotation for improving continuity of care in a surgical training program.

The modern resident team, staffed by multiple attendings, often makes sacrifices on continuity of care due to scheduling conflicts. We investigated a one-on-one mentor-resident rotation where all clinical activities were synchronized to produce near-perfect continuity of care, and we compared the objective and subjective outcome measures to those of control rotations of the same resident during the same year. The results showed that continuity of care close to 100% was possible in such rotations, but work hours were increased by 25%. Also, the number of patients seen was decreased by over 50%. The rotation was well-received by both mentors and residents. Continuity of care per se can be improved by this rotation. However, theoretical disadvantages, mainly narrow training due to exposure to only one mentor and fewer patients, make it unsuitable for extended use.

General Surgery↗
PubMed1997

A case-controlled study of laparoscopic splenectomy.

BACKGROUND: The utility of laparoscopic splenectomy (LS) has not been tested in general surgical practice. This is a case controlled study comparing the clinical results and economics of L.S. and open splenectomy (OS) in a community hospital. METHODS: The outcome of a series of 15 patients undergoing LS were compared to 15 patients undergoing OS matched for diagnosis, splenic weight, age, and main co-morbidites, selected by a person independent of the project. RESULTS: In both series, the indications were immune thrombocytopenic purpura, hemolytic anemias, hairy cell leukemia and, staging for Hodgkin's disease. LS resulted in shorter hospitalization (2.3 vs 8.8 days) with fewer postoperative complications. However, the operation was 1.7 times as long, and the operating room charge 2.9 times as high, so that the total cost of LS ($18,015) was greater than that for OS ($14,524). If the cost of treatment of complications is included, then the total is the same for both at our institutions. CONCLUSION: Except for a few indications not addressed in this study, LS can be used in lieu of OS.

Case-Control Studies↗