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Biomedical subjects

R Blanco

Publications and source records attributed to R Blanco.

At least 127 records · Page 7Linked to original sources

Transforming growth factor-alpha immunoreactivity in the developing and adult brain.

Transforming growth factor-alpha immunoreactivity is examined in the developing and adult brain of cats and rats, and in the adult human brain in cryostat sections immediately processed free-floating with a well-characterized monoclonal antibody which does not cross-react with epidermal growth factor. Transforming growth factor-alpha immunoreactivity is observed in neurons of the cerebral neocortex, subiculum, hippocampus, striatum, thalamus, amygdala, basal forebrain, mesencephalon, cerebellar cortex, dentate nucleus and brainstem during development and in adulthood. The intensity of the immunoreaction directly correlates with the size of the cytoplasm. Diffuse transforming growth factor-alpha immunoreactivity also occurs in the white matter of the cerebrum, cerebellum and brainstem in the kitten, but not in the adult cat. In addition to neurons, numbers of glial cells in the cerebellar white matter, brainstem and cerebral hemispheres during development, and a few glial cells in the cerebellar cortex, diencephalon, cerebral cortex and white matter in adults are strongly transforming growth factor-alpha immunoreactive. These results support the concept that transforming growth factor-alpha is widely distributed in the brain of mammals, localizes in both neurons and glial cells, and is development dependent. These findings also suggest that transforming growth factor-alpha may play a role in the developing and adult central nervous system.

Adult↗

Evidence of internucleosomal DNA fragmentation and identification of dying cells in X-ray-induced cell death in the developing brain.

Newborn Sprague-Dawley rats received a single dose of 2 Gy X-rays and were killed 6 hr later. Dying cells were characterized by extreme chromatin condensation and nuclear fragmentation. Dying cells were distributed in the primary and secondary germinal zones and in other brain regions. Among these latter, dying cells occurred in the cortical layers of the olfactory bulb, layers II-III and VIb of the neocortex, piriform and entorhinal cortex, stratum oriens and pyramidale of the hippocampus, striatum, thalamus, amygdala, brainstem, internal granular layer of the cerebellum, and cerebral and cerebellar white matter. Dying cells were immature cells, neurons and glial cells (including radial glia). In-situ labeling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. Since the number of cells stained with this method was larger than the number of dying cells, as revealed with current histological techniques, it is suggested that nuclear DNA fragmentation precedes chromatin condensation and nuclear fragmentation in X-ray-induced apoptosis. Furthermore, agarose gel electrophoresis of extracted DNA from irradiated brains showed a "ladder" pattern which is typical of internucleosomal DNA fragmentation and endonuclease activation.

Aging↗

Acute reversible hypoxemia in systemic lupus erythematosus: a new syndrome or an index of disease activity?

In 1991, Abramson et al reported a new syndrome of acute reversible hypoxemia (ARH) in patients with severe SLE (systemic lupus erythematosus). This syndrome was characterized by an unexplained abnormal value of arterial blood gases (ABG) without obvious parenchymal lung disease, and a good response to high-dose corticosteroid therapy. After we became aware of this entity, four of 16 patients admitted to our unit because of a SLE flare presented respiratory symptoms and abnormal ABG consistent with ARH. In none of our patients were the pulmonary manifestations a prominent clinical feature of the disease. Furthermore, in two of them, treatment with high-dose aspirin and moderate to low doses of corticosteroids was sufficient to improve the pulmonary manifestations, but not to control the systemic activity of the disease. Therefore, we believe that this new pulmonary finding more than a clinically independent syndrome represents an index of disease activity in patients with SLE.

Acute Disease↗

Tooth malalignments in Chilean children with Down syndrome.

The present study analyzes the frequencies and types of anomalies in tooth alignment in a sample of 136 children with Down syndrome, 147 mentally-impaired individuals without Down syndrome, and 149 normal individuals. Patients with Down syndrome showed a higher frequency of malalignments in both the deciduous and permanent dentitions compared with the children in control groups. In the three groups studied, the frequency of malalignments was higher in the permanent than in the deciduous dentition. In the deciduous dentition, the frequency of malalignments in the three groups was similar in the maxilla and mandible, and in both boys and girls. In the permanent dentition, the frequency of malalignments was higher in Down and mentally-impaired girls without Down syndrome, while the frequency of malalignments in the mandible was only increased in mentally-impaired individuals who did not have Down syndrome. In the deciduous dentition, the Down group presented a higher frequency of malalignment in the upper central incisor, lateral incisor, and canine regions compared with the normal children. When comparing teeth of Down children with those of mentally-impaired individuals who did not have Down syndrome, differences in malalignment were observed only in upper central incisor and canine regions. In the permanent dentition, the Down group showed a higher number of tooth malalignments than the normals (13 out of 28 teeth). A comparison of Down with non-Down mentally-impaired individuals, revealed only 8 teeth out of 28 were different. The most frequent malalignments in the deciduous dentition in Down patients were mesiopalatal, mesiolingual, and mesiovestibular. In the permanent dentition, the most frequent malalignments were distopalatal or distolingual.

Case-Control Studies↗

Cell death induced by gamma irradiation of developing skeletal muscle.

Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 microgram/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle.

Animals↗

Ubiquitinated structures in the white matter of the gerbil following chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion was produced in adult gerbils aged 3-6 months following bilateral stenosis of the carotid artery lasting 8 weeks. Animals with no evidence of cerebral infarction were used in the present study. Ubiquitin-immunoreactive free granules in the subcortical cerebral white matter and corpus callosum were observed in five of 12 animals. No similar lesions were found in sham-operated animals, age-matched controls, and gerbils subjected to transient forebrain ischaemia for 20 min and killed at different intervals. These results indicate that diffuse damage of the subcortical white matter may be encountered as the only neuropathological change following chronic hypoperfusion.

Animals↗

Naturally occurring cell death in the developing cerebral cortex of the rat. Evidence of apoptosis-associated internucleosomal DNA fragmentation.

Naturally occurring dead cells in the developing rat neocortex, subcortical white matter and hippocampus, which increase in number during the first postnatal week and decrease thereafter to disappear by the end of the first month, were examined by in situ labeling of nuclear DNA fragmentation. These cells showed peripheral chromatin condensation or extremely dark, often fragmented, nuclei. Southern hybridization following agarose gel electrophoresis of DNA extracted from the developing cortex, but not from adult brain, showed a 'ladder' pattern which is typical of internucleosomal DNA fragmentation. Taken together these results show that naturally occurring cell death (programmed cell death) in the developing cerebral cortex has the morphology of apoptosis and is associated with endonuclease activation.

Aging↗

Increased expression of bcl-2 immunoreactivity in the developing cerebral cortex of the rat.

Bcl-2 proto-oncogene encodes a protein which may cancel the cell death programme in normal development and experimentally induced conditions. Strong bcl-2 immunoreactivity occurs in the neocortex and hippocampus of the developing rat during the 1st postnatal week. Bcl-2 immunoreactivity rapidly decreases from this age onwards to steady very low levels in adulthood. Since increased expression of bcl-2 immunoreactivity during cortical neurogenesis is coincidental in time with a special vulnerability of cortical neurons to naturally occurring cell death, it is suggested that bcl-2 may have a role in regulating cell death and survival during cortical morphogenesis.

Animals↗

The use of a bone peg in the Sauvé-Kapandji operation.

The use of a bone peg for fusion of the distal radio-ulnar joint as part of the Sauvé-Kapandji procedure is described. This has been used effectively in six patients, one of whom developed a painless pseudoarthrosis after a fall.

Adult↗

Evidence of nuclear DNA fragmentation following hypoxia-ischemia in the infant rat brain, and transient forebrain ischemia in the adult gerbil.

Wistar rats, eight days old, were subjected to permanent bilateral forebrain ischemia, followed by hypoxia for 15 minutes. A cerebral infarct, mainly involving the cerebral neocortex, hippocampus, amygdala, striatum and subcortical white matter was produced. Neurons and glia showing punctate chromatin condensation and karyorrhectic cells were observed 12 hours after hypoxia-ischemia. Their number increased during the first two days and recruitment of cells with degenerating nuclei occurred until day five. In situ labeling of nuclear DNA fragmentation stained many normal-appearing nuclei, as well as punctate chromatin condensations and nuclear fragments in karyorrhectic cells. Delayed neuronal death in the CA1 area of the hippocampus was observed after 20 minutes of transient forebrain ischemia in the adult gerbil. In situ labeling of nuclear DNA fragmentation demonstrated stained punctate chromatin condensation in a few degenerating cells at 48 hours post-ischemia. Substantial labeling of CA1 neurons occurred in the fourth day. Agarose gel electrophoresis of extracted brain DNA from ischemic infant rats and adult gerbils showed a ladder-type pattern which is typical of nuclear DNA fragmentation into oligonucleosomal fragments (internucleosomal cleavage). These findings suggest that endonuclease(s) activation may play a role in cell death induced by different forms of hypoxia-ischemia.

Animals↗

Malignant ventricular arrhythmia in systemic sclerosis controlled with an implantable cardioverter defibrillator.

The prognosis of systemic sclerosis (SSc) is poor, and a significant number of patients suffer sudden death, probably related to malignant ventricular arrhythmias for which there is no reliable drug treatment. We describe a patient with SSc who had 2 documented episodes of ventricular fibrillation, that reverted after electrical defibrillation. An electrophysiological study performed after 3 weeks of oral loading with amiodarone 1200 mg/day, demonstrated the induction of unstable sustained syncopal ventricular tachycardia. She has been successfully controlled with the implant of a 3rd generation implantable cardioverter defibrillator. We suggest that this treatment should be seriously considered in those patients with SSc and malignant ventricular arrhythmias unresponsive to drug therapy.

Adult↗

Unresectable nonmetastatic squamous cell carcinoma of the esophagus managed by sequential chemotherapy (cisplatin and bleomycin) and radiation therapy.

BACKGROUND: For patients with unresectable nonmetastatic squamous cell carcinoma of the esophagus (SCCE), the conventional treatment has been radiation therapy (RT). Because RT alone is unsatisfactory, there has been increasing interest in including chemotherapy (CT) in the management of these patients. METHODS: Twenty-five previously untreated patients with unresectable nonmetastatic SCCE were treated with sequential CT and RT. CT consisted of cisplatin 35 mg/m2/day for 3 days plus bleomycin 15 mg/day for 3 days as an 18-hour infusion every 3 weeks. After three courses of CT, RT was administered (dose, 200 rads/day with a planned total dose of 50-60 Gy). RESULTS: Nineteen tumors were T3; six were T2 and larger than 7 cm. Fifteen patients (60%) had severe dysphagia that required placement of nasogastric tubes in 14 and gastrostomy in 1. All patients were evaluable for response. Thirteen patients (52%) had a partial response to CT. After combined treatment, four patients had complete responses (16%), and nine had partial responses (36%; overall response rate, 52%). The median survival was 8 months; 20% were alive at 1 year, and 8% lived more than 4 years. The median survival for responders to CT was 8 months compared with 5 months for nonresponders (P = 0.005). Combined treatment improved dysphagia in 16 patients (64%) with complete resolution in 13. Toxicity was mild. CONCLUSIONS: The use of sequential CT (cisplatin and bleomycin) and RT in this group of patients is feasible; there is little additional toxicity, and good palliative effects can be achieved. The patient's response to CT is a good prognostic factor. The development of more effective combinations that induce more durable responses and higher rates of complete response are required.

Aged↗

The sequence of eruption of the permanent dentition in a Chilean sample with Down's syndrome.

The eruption of the permanent teeth in Down's individuals is reportedly delayed. The extent of such delay in comparison to normal children has been little studied. The eruption characteristics of the permanent teeth in a sample of Chilean individuals with Down's syndrome were here compared with those of the normal Chilean population. The sample consisted of 240 Down's individuals (all with trisomy 21), 116 males and 124 females. The chronological sequence of eruption in Down's children was not completely different from the normal. The least affected teeth were upper and lower first molars and central and lateral incisors. Alterations of the eruption sequence were not necessarily a consequence of alterations in the time of eruption. Asymmetries between sides of the jaw were mainly in canines and premolars. Alterations in sequence timing and asymmetry seem to be age dependent, being less frequent between 7 and 9 yr of age and more frequent between 10 and 14 yr of age. This may also reflect the larger variances of age of eruption observed in Down's individuals. Despite this, Down's children maintained a certain similarity in sequence and symmetry in comparison to normals.

Adolescent↗

Treatment of stage I testicular tumours.

Between 1980 and 1989, 138 patients with stage I carcinoma of the testes were treated and followed up; 81 patients had seminoma and 57 had non-seminomatous tumours. Between January 1980 and December 1983, patients with seminoma were treated by orchiectomy, followed by complementary radiotherapy to aortic and ipsilateral pelvic nodes. Retroperitoneal lymph node dissection (RPLND) was performed in patients with non-seminomatous tumours. After January 1984 the treatment strategy was changed and orchiectomy was followed by a surveillance policy in all histological types. In seminoma patients, 1 of 36 patients (3%) treated with complementary radiotherapy and 5 of 45 (11%) on the surveillance policy relapsed. All achieved a complete response after chemotherapy. In non-seminomatous tumours, 3 of 21 patients (14%) treated with complementary lymphadenectomy relapsed, in contrast to 11 of 36 (31%) surveillance policy patients. All patients who relapsed obtained a complete response with chemotherapy. All patients are currently free of disease. There were no differences in survival between both treatment policies. We conclude that a wait and see policy in stage I testicular tumours is feasible and provides the same results as more interventionist practices.

Combined Modality Therapy↗