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Biomedical subjects

L Rodriguez

Publications and source records attributed to L Rodriguez.

At least 37 records · Page 2Linked to original sources

Purification and characterization of the invertase from Schizosaccharomyces pombe. A comparative analysis with the invertase from Saccharomyces cerevisiae.

Invertase (EC 3.2.1.26) was purified to homogeneity from exponentially growing cells of Schizosaccharomyces pombe fully de-repressed for synthesis of the enzyme, and was shown to be a high-molecular-mass glycoprotein that can be dissociated in the presence of 8 M-urea/1% SDS into identical subunits with an apparent molecular mass of 205 kDa. The carbohydrate moiety, accounting for 67% of the total mass, is composed of equimolar amounts of mannose and galactose. There is a small amount of glucosamine, which is probably involved in the linkage to the protein moiety, since the enzyme is sensitive to treatment with endoglycosidase H. The composition of the carbohydrate moiety resembles that found in higher-eukaryotic glycoproteins and differs from glycoproteins found in Saccharomyces cerevisiae. The protein portion of each subunit is a polypeptide of molecular mass 60 kDa, very similar to the invertase of Sacch. cerevisiae. Both proteins cross-react with antibodies raised against the protein fractions of the other, indicating that the two enzymes are similar.

Carbohydrates

Current state of the hybridoma technology.

The first description of the hybridoma technology in 1975 seemed to hold enormous promise for the treatment of a variety of human disease. The ability to produce monoclonal antibodies led to the availability of large amounts of homogeneous and predictable preparations of antibody. The potential to renew indefinitely a particular antibody surmounted many of the technical and regulatory problems that made polyclonal antisera difficult to use as therapeutic agents in man. The hybridoma technology seemed even more valuable as it became clear that it could lead to the generation of pure, highly specific antibodies from impure, poorly characterized antigens. Monoclonal antibodies have been extremely useful in basic investigations and have facilitated the development of new diagnostic tests for serum and tissue components and infectious agents. However, novel approaches are needed in order to provide more useful, less immunogenic antibodies which could be used routinely for passive immunization in the treatment of infections or for tumor targeting.

Animals

Prevention of high altitude-induced testicular disturbances by previous treatment with cyproheptadine in male rats.

Male rats were exposed to 4,340 m altitude for 4 days. At this time histological alteration in the testes were observed. There were tubules with pyknotic primary spermatocytes and spermatids, necrosis of numerous cells, and sloughing of primary spermatocytes. The damaged areas were limited by normal tissue. Serum testosterone increased significantly after 4 days of exposure. Administration of an anti-serotoninergic compound, cyproheptadine (10 mg/kg body weight), prevented the high altitude-induced changes in both spermatogenesis and serum testosterone. These observations suggest that serotonin is involved in the testicular changes that occurred when rats are acutely exposed to high altitude.

Altitude Sickness

[Mammaplasty on breast implants (or cutaneous expansion in treating distended skin)].

The authors present their experience of the use of skin expansion in secondary surgery to previously implanted breasts. This technique constituted a relatively simple solution with minimal scarring for certain cases in which the residual breast volume was insufficient or non-existent and in which it was impossible to reconstruct a breast with acceptable shape and volume after removal of the implant.

Female

Giant-cell tumor of the sphenoid bone: case report and review of the literature.

We report the case of a 23-year-old man with a giant-cell tumor of the sphenoid bone. The radiologic manifestations consisted of an expansile mass arising from the sphenoid bone with extension into the cranial cavity and the nasopharynx. The findings with computed tomography and magnetic resonance imaging best reflected respectively the osseous and soft-tissue extent of the disease.

Adult

Phase I/II study of intraventricular and intrathecal ACNU for leptomeningeal neoplasia.

A total of 27 patients with leptomeningeal neoplasia were treated with the water-soluble nitrosourea ACNU given intraventricularly or intrathecally in a phase I/II study. Patients were entered in the study if they showed evidence of either a positive CSF cytology or neurodiagnostic evidence of leptomeningeal disease, or both. Patients were evaluated for toxicity and efficacy; additionally, in 13 patients ACNU pharmacokinetic studies were carried out. A variety of tumor types were represented in the study group, including primary and metastatic CNS tumors. Toxicity was mild and included pain at the injection site (four patients), transient radicular symptoms at a short distance from the injection site (three patients), and nausea and vomiting (one patient). No myelotoxicity was seen. Of 21 patients who presented with positive cytology, 8 (38%) had a conversion from positive to negative cytology, with a range of response durations from 1 to 20+ months. Of the remaining six patients with negative cytology but other neurodiagnostic evidence of leptomeningeal disease, one patient showed an improvement seen on the myelogram and one underwent a brief reduction in CSF protein. ACNU elimination from the ventricular system is rapid, with a beta slope of 0.028 min-1 and a computed elimination constant, Ko of 13 min. The mean clearance was 3.8 ml/min (range, 1.0-6.2 ml/min). Peak ACNU levels varied between 108 and 620 micrograms/ml, with the AUC being 1.4-14.7 mg.min/ml. The total dose of ACNU given was between 9 and 104 mg, and the single dose range was 4-16.5 mg. We conclude that ACNU can be given safely with minimal toxicity as intra-CSF therapy, that it demonstrates efficacy in some patients with leptomeningeal disease, and that further studies are warranted to evaluate more fully alternative dosing and drug delivery approaches.

Arachnoid

Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine.

Thirty-eight patients with primary recurrent anaplastic gliomas and glioblastomas, were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the polyamine inhibitor alpha-difluoromethylornithine (DFMO). There were 5 brain stem, 1 cerebellar, and 32 supratentorial glioma tumors. All had been treated with surgery (except in the case of 4 brain stem tumors for which biopsies were not obtained) and radiotherapy. Eight patients had received prior chemotherapy. Of the 21 patients with evaluable supratentorial anaplastic gliomas, 2 (9.5%) had a partial response and 10 (47.6%) had stable disease. The median time to tumor progression for the anaplastic gliomas has not been attained yet. However, median survival for these 12 patients was 119 weeks measured from the initiation of chemotherapy. Median survival for the entire anaplastic glioma group of 21 was 56 weeks. Minimal activity was seen against glioblastoma multiforme. The median time to tumor progression was 8 weeks with median survival of 21 weeks. Of the 5 patients with brain stem tumors, 3 are alive with stable disease at 77, 93, and 220 weeks. The combination was well tolerated with dose-limiting toxicity being myelosuppression and hearing loss. Further trials are warranted to compare the combination of BCNU and DFMO against BCNU alone in a prospective randomized trial.

Antineoplastic Combined Chemotherapy Protocols

Mechanical failure of the Björk-Shiley valve. Updated follow-up and considerations on prophylactic rereplacement.

The early production series of the 29 to 31 mm 70-degree convexo-concave (CC70) Björk-Shiley heart valves constitutes a subgroup of CC70 values with an extra high risk of outlet strut fracture. The hazard function for mechanical failure among these valves has remained almost constant over a 7-year follow-up period, and the 7-year actuarial incidence of mechanical failure among these valves is 12.5%. Selected patients with these valves will be considered for prophylactic rereplacement.

Aortic Valve

Valsalva maneuver: a test of the functional state of cardiac innervation in Chagasic myocarditis.

The ratio between maximal and minimal R-R intervals measured during the Valsalva maneuver is an adequate means of studying the functional state of the cardiac parasympathetic nervous system. We studied the changes in heart rate evoked during the Valsalva maneuver in 49 asymptomatic Chagasic patients with different degrees of myocardial involvement. The Chagasic patients were divided in three groups. Twelve patients had no evidence of heart disease except for an abnormal myocardial biopsy. Sixteen patients had a normal electrocardiogram but revealed evidence of localized myocardial damage as shown by left ventricular cineangiography. Twenty-one patients had abnormal electrocardiograms and revealed multiple areas of abnormal left ventricular wall motion. The Valsalva ratio (mean +/- standard error) was 1.62 +/- 0.12 for controls, 1.52 +/- 0.10 for those with an abnormal biopsy, 1.48 +/- 0.06 for those with localized myocardial damage, and 1.31 +/- 0.04 for those with an abnormal electrocardiogram. There were no statistically significant differences between the control group (normal sero-negative subjects) and those patients with normal electrocardiograms. Results in those with an abnormal electrocardiogram, however, were statistically different (P less than 0.05) from the other groups. These results are in discordance with the commonly accepted hypothesis that cardiac parasympathetic denervation causes a dilated myocardiopathy in patients with chronic Chagasic myocarditis.

Adult

Aortic origin of the right pulmonary artery: a cause of heart failure in infancy at high altitude.

The development of technique for surgical correction of aortic origin of the right pulmonary artery is described. In the first patient, aged 7 years, the operation was performed via bilateral thoracotomy, with standby for extracorporeal circulation, and the right pulmonary artery was anastomosed directly to the left, using side clamps on both aorta and left pulmonary artery. The currently preferred procedure is to operate as early as possible in infancy, using perfusion at 30 degrees C with ventricular fibrillation and without cross-clamping of the aorta. Wide mobilization of the pulmonary artery probably prevents stenosis at the end-to-side anastomosis.

Altitude

Nitrogen bridgehead compounds. 66. Bronchodilator nitrogen bridgehead compounds with a pyrimidinone moiety.

New types of bronchodilator agents, bi- and tricyclic nitrogen bridgehead compounds with a pyrimidin-4(3H)-one ring, were synthesized and evaluated for bronchodilator activity against serotonin-, histamine-, and acetylcholine-induced spasms in the guinea pig Konzett-Rössler test. The structure-activity relationships are discussed. The effects of some bi- and tricyclic derivatives on the human bronchus were also investigated. The homologous tricyclic compounds 68 and 69 were tested on isolated guinea pig ileum and trachea, and the effects of compound 69 were investigated in pilocarpine-treated dogs. Azepino[2,1-b]quinazoline (69; CHINOIN-1289) was selected for further biochemical and clinical investigations.

Animals