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Biomedical subjects

R Gonzalez

Publications and source records attributed to R Gonzalez.

At least 433 records · Page 24Linked to original sources
PubMedDate not supplied

Metabolic control analysis of monoclonal antibody synthesis.

A general route for protein synthesis in eukaryotic cells has been proposed and applied to monoclonal antibody (MAb) synthesis. It takes into account transcription of the gene, binding of ribosomes to mRNA, and polypeptide elongation including binding to SRP (signal recognition particles) and SRP-receptor, competing translocation, folding and glycosylation, assembly of the heavy and light chains in a tetrameric protein and Golgi processing and secretion. A comprehensive model was built on the basis of the proposed pathway. The model takes into account the mechanism of each step. Metabolic control analysis (MCA) principles were applied to the general pathway using the proposed model, and control coefficients were calculated. The results show a shared flux control (of both pathway flux and flux ratio at the branch) among different steps, i.e., transcription, folding, glycosylation, translocation and building blocks synthesis. The steps sharing the control depend on the concentration of building blocks, pathway flux and levels of OST (oligosacharyl transferase), BiP (heavy chain binding protein) and PDI (protein disulfide isomerase). Model predictions compare well with experimental data for MAb synthesis, explaining the control structure of the route and the heterogeneity of the product and also addressing future targets for improvement of the production rate of MAbs.

Antibodies, Monoclonal↗
PubMedDate not supplied

Single barbed stainless steel coils for venous occlusion: a simple but useful modification.

Embolization of coils into the lungs has been reported following their use for the obliteration of large arteriovenous fistulas. So far, except for a recent report, they have not been used on the venous side of the circulation. Experimental studies at our institution demonstrated that the placement of coils on the venous side can result in embolization to the lungs, even when oversized coils are introduced. A simple, easy to perform modification of the standard stainless steel coils (Gianturco-Wallace-Chuang spring embolus and coilons) makes these devices safe embolic agents for used on the venous side of the circulation, as for example in the obliteration of spermatic veins.

Animals↗
PubMedDate not supplied

Melatonin therapy of advanced human malignant melanoma.

We undertook a study to investigate the therapeutic potential of orally administered melatonin in patients with advanced melanoma. Forty-two patients received melatonin in doses ranging from 5 mg/m2/day to 700 mg/m2/day in four divided doses. Two were excluded from analysis. After a median follow-up of 5 weeks, six patients had partial responses, six additional patients had stable disease. Sites of response included the central nervous system, subcutaneous tissue and lung. The median response duration was 33 weeks for the partial responders. There was a suggestion of a dose-response relationship. The toxicity encountered was minimal and consisted primarily of fatigue in 17 of 40 patients. Melatonin also appeared to reduce basal levels of follicle-stimulating hormone (FSH). No significant changes were encountered in serum levels of luteinizing hormone (LH) or thyroid stimulating hormone (TSH). We conclude that further study of melatonin as a potentially useful agent in metastatic melanoma is warranted.

Adolescent↗
PubMedDate not supplied

Pediatric melanoma: are recent advances in the management of adult melanoma relevant to the pediatric population.

PURPOSE: Although melanoma in childhood is a rare condition, there is evidence that it is increasing in frequency. As advances are being made in the understanding and therapy of adult melanoma, we need to consider the relevance of these advances to the pediatric population. PATIENTS AND METHODS: We have reviewed our experience at the University of Colorado Health Sciences Center with the clinical parameters, therapy, and outcomes of melanoma in 27 patients age 16 years or younger and contrasted these to the adult experience. RESULTS: Most cases were diagnosed early with the median thickness of the primary melanoma being 0.75 mm. Six of seven patients who had lymph node metastases develop remain alive at a median follow-up of 62 months. Durable complete responses to a variety of therapies were seen in three of five patients with advanced disease outside the central nervous system. Our experience with sentinel node biopsy, adjuvant interferon, and new therapies for metastatic melanoma were also reviewed and appear to be relevant for younger patients. CONCLUSIONS: The behavior of melanoma in the pediatric population at our center is similar to that seen in adults. The integration of recent advances in the staging and therapy of melanoma in adults would be of benefit to children with this condition.

Adolescent↗
PubMedDate not supplied

Review of tests for monitoring doxorubicin-induced cardiomyopathy.

The objective of this review is to make physicians aware of new radionuclide methods to detect cardiac effects of chemotherapeutic drugs. This knowledge is important because of the limitations of the physical examination and the electrocardiogram for detecting early reversible cardiac damage. Presently left ventricular ejection fraction (LVEF) is routinely used to screen for cardiotoxicity. Since LVEF obtained by radionuclide angiocardiography is more accurate than the LVEF estimated by echocardiography, serial radionuclide LVEF monitoring is most commonly used to monitor cardiotoxicity. Diastolic measurements of left ventricular function (such as peak filling rate) are now being added to routine LVEF measurements to enhance standard radionuclide evaluation. This screening test should be done prior to beginning therapy and at appropriate points based on the baseline study, therapy scheme and the patient's clinical status. At some centers, exercise LVEF methods are being used to determine if cardiac reserve is adequate for the patient to tolerate additional chemotherapy when cardiac injury may be present. Previously, endomyocardial biopsy was needed to detect and confirm early anthracycline cardiotoxicity. This invasive test may be replaced by a new noninvasive in vivo method using radioactive monoclonal antibodies against cardiac muscle (indium-111-antimyosin). Because cardiac failure has been associated with adrenergic neuron injury, it has been proposed that radioactive methyliodobenzylguanine may detect the adrenergic abnormality which may predict future development of congestive heart failure or sudden death months after therapy is discontinued. Advantages and disadvantages of these methods in evaluating cardiotoxicity, and an algorithm to optimally monitor antitumor therapy-induced cardiomyopathy are discussed.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Use of urinary beta-2-microglobulin to predict severe renal damage in fetal obstructive uropathy.

PURPOSE: Establish a clinically relevant threshold for urinary beta 2-microglobulin (beta 2m) to predict the presence of several renal damage in fetuses with obstructive uropathies. METHODS: Retrospective review was conducted of urinary beta 2m levels, clinical outcomes, and pathological findings in 36 fetuses evaluated for presumed obstructive uropathy. Patients were divided into those free of renal injury (group 1, n = 13) and those with clinical or pathological evidence of severe irreversible renal injury (group 2, n = 23). RESULTS: Including all patients, a threshold beta 2m value of > 6 was able to predict the presence of severe renal damage with a 83% sensitivity and 71% specificity. beta 2m levels tended to decrease with increasing gestational age among those patients without renal injury (group 1), while beta 2m levels increased among those with severe renal damage (group 2). There was no difference in mean beta 2m levels in those < 20 weeks (p = 0.065) while there was a high degree of difference in those > 20 weeks of gestation (p < 0.001). In those > 20 weeks, a threshold of > 10 predicted the presence of severe renal damage with 100% sensitivity and specificity. CONCLUSIONS: Urinary beta 2m, especially in the fetus > 20 weeks, may be a clinically useful marker to detect the presence of severe renal damage due to obstructive uropathy and thus be an important adjuvant in the proper selection of fetuses for antenatal intervention.

Creatinine↗
PubMedDate not supplied

Androgen directs apparent cytoplasmic and nuclear distribution of rat cardiovascular androgen receptors.

We used either the synthetic androgen R1881 (methyltrienolone) or 5 alpha-dihydrotestosterone (5 alpha-DHT) to characterize androgen receptors in rat aortic and myocardial cytoplasmic and nuclear preparations. Relative steroid specificity studies established that only androgens were effective inhibitors of R1881 (cytoplasmic) or 5 alpha-DHT (nuclear) binding to aortic and myocardial androgen receptors, whereas estrogens, progestins, and cortisol were ineffective inhibitors. Low ionic strength sucrose density gradient centrifugation analyses showed that androgen receptors in aortic and myocardial cytoplasmic preparations migrated as macromolecules with sedimentation coefficients of 8 to 9S, whereas androgen receptors in aortic and myocardial nuclear preparations migrated as macromolecules with sedimentation coefficients of 4 to 5S (high ionic strength buffer). Saturation analyses established that aortic and myocardial cytoplasmic preparations from intact, untreated young mature female rats contained 45.8 +/- 9.7 (mean +/- SD) and 63.3 +/- 20.7 fmol androgen receptor/mg DNA, respectively. The respective R1881 dissociation constants were 0.60 and 0.32 nM. Androgen receptors could not be demonstrated in nuclear preparations from the cardiovasculature of intact females. Testosterone injection of intact young mature female rats caused apparent depletion of androgen receptors in aortic and myocardial cytoplasmic preparations and resulted in concomitant appearance of 57.1 +/- 22.2 and 52.3 +/- 21.5 fmol receptor/mg DNA in the corresponding nuclear preparations. The respective 5 alpha-DHT dissociation constants were 4.46 and 1.63 nM. The ability of testosterone to affect apparent intracellular distribution of cardiovascular androgen receptors suggests that the receptors are physiologically functional and indicates that androgen may directly regulate cardiovascular cell function.

Androgens↗
PubMedDate not supplied

Estradiol-17 beta affects estrogen receptor distribution and elevates progesterone receptor content in baboon aorta.

We used the synthetic estrogen R2858 (moxestrol) and estradiol-17 beta, respectively, to characterize the estrogen receptor in baboon (Papio sp.) aortic or myocardial cytoplasmic and nuclear preparations. We observed regional differences in the cytoplasmic fraction estrogen and progesterone receptor content of aortic arch, thoracic aorta, and abdominal aorta when tissues from either oophorectomized or oophorectomized estradiol-17 beta-treated subjects were compared. The estrogen receptor content was highest in the abdominal aorta and lowest in the aortic arch. In contrast, the cytoplasmic fraction progesterone receptor content was highest in the aortic arch and lowest in the abdominal aorta. The nuclear fraction estrogen receptor could not be demonstrated in preparations from cardiovasculature of oophorectomized female baboons. The use of Silastic implants to administer a physiologic concentration of estradiol-17 beta to oophorectomized female baboons caused a 20% to 50% reduction in cytoplasmic fraction estrogen receptor content, which was quantitatively accounted for by the appearance of estrogen receptor in the corresponding nuclear aortic or myocardial preparation. Estrogen administration caused a 20% to 40% increase in cytoplasmic fraction progesterone receptor content in both myocardium and aorta; however, differences were significant only for abdominal aorta (p less than 0.05). Estradiol-17 beta treatment caused a tenfold increase in uterine cytoplasmic fraction progesterone receptor content in treated as compared to oophorectomized control females, suggesting that baboon cardiovasculature is less sensitive to changes in endogenous estrogen concentration than is uterus. The ability of estradiol-17 beta to affect apparent intracellular distribution of baboon cardiovascular estrogen receptors and to elevate cytoplasmic fraction progesterone receptor content suggests that these estrogen receptors are physiologically functional and indicates that estrogen may directly regulate primate cardiovascular cell function.

Animals↗
PubMedDate not supplied

Gender and baboon aortic steroid hormone receptors.

To examine the potential of steroid hormones to serve as putative regulators of aortic cell function, we defined hormone receptor content and distribution in intact baboons. Total androgen receptor content in baboon aortic arch, thoracic arch, and abdominal aorta of young mature males was indistinguishable from that of proestrus females. However, 30% to 40% of male aortic androgen receptors were in the nuclear fraction, whereas all aortic androgen receptors of proestrus females were in the cytoplasmic fraction. Cytoplasmic fraction estrogen receptor content of aortic arch and thoracic aorta of intact males was indistinguishable from that of proestrus females. However, cytoplasmic fraction estrogen receptor content of abdominal aorta of proestrus females was significantly greater than that of males. Nuclear fraction estrogen receptors were not detectable in either male or proestrus female baboon aortas. To assess effects of endogenous estrogen on aortic progesterone receptor content, we quantified cytoplasmic fraction progesterone receptors and found that content of proestrus female aortic arch was not significantly different from that of males. However, cytoplasmic fraction progesterone receptor content of thoracic and abdominal aorta of proestrus females was significantly higher than that of males. To determine whether differences in aortic receptor content or distribution were associated with changes in aortic cell function, we quantified the activity of two enzymes of glycosaminoglycan metabolism. Aortic beta-glucuronidase activity was not different in male or proestrus female baboons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Prevention of highly emetogenic chemotherapy-induced vomiting: a double blind, randomized crossover study to compare pancopride (LAS 30451) and pancopride plus dexamethasone.

AIMS: Pancopride (PNC) is a new 5HT3 receptor antagonist which has demonstrated complete protection from nausea and vomiting in 25-73% of patients treated with highly emetogenic chemotherapy. A double-blind, randomized crossover study was carried out to assess whether the addition of dexamethasone (DXM) to PNC increases the antiemetic efficacy. METHODS: PNC (0.2 mg/kg. i.v. 30 min before chemotherapy) plus placebo (PLC) was compared with PNC (same dose and schedule) plus DXM (20 mg. i.v. immediately before PNC). In the second cycle, patients received the alternative antiemetic treatment. Eighty patients were included in the study (PNC + DXM = 39, PNC + PLC = 41), 29 of whom were women and 51 men. Fifty-four percent of the patients in the PNC + DXM group and 59% of those in the PNC + PLC group received chemotherapy containing cisplatin. Seventy-seven patients completed the first cycle and 70 the second. RESULTS: Complete protection was obtained in 19/16 patients (50/46%) with PNC + PLC and in 32/22 (82/63%) with PNC + DXM (P < 0.001). Latency was significantly longer in the PNC + DXM group. The efficacy of both treatments was unaffected by the order of administration. Side effects were mild in both groups. CONCLUSIONS: The combination of PNC + DXM is more efficacious than PNC + PLC in protection against highly emetogenic chemotherapy-induced vomiting.

Antiemetics↗
PubMedDate not supplied

Man-biting activity of Anopheles (Nyssorhynchus) albimanus and An. (Kerteszia) neivai (Diptera: Culicidae) in the Pacific lowlands of Colombia.

The daily man-biting activity of Anopheles (Nyssorhynchus) albimanus and An. (Kerteszia) neivai was determined in four ecologically distinct settlements of the Naya River, Department of Valle, Colombia. Differences were found among the settlements with respect to the mosquito species present, intradomiciliary and extradomiciliary biting activity and population densities.

Animals↗
PubMedDate not supplied

Long-term outcome of one haploidentical live related donor transplantation in children.

UNLABELLED: We report on 69 children, 6 months to 18 years old, who received a one-haploidentical live related donor transplantation from 11/72 through 4/89. Thirty patients were maternal and 22 were paternal recipients; 23 were Black, 27 Caucasian, 17 Hispanic, and 1 each Oriental and Arabic. The original diagnoses in these patients were aplastic/dysplastic kidneys 13%, obstructive uropathy 30%, focal segmental glomerulosclerosis (FSGS) 23% and lupus nephritis 10%. RESULTS: 1-, 5-, 10- and 15-year actuarial patient and graft survivals were 98, 84, 84, 84% and 94, 70, 41, 30% respectively. Actual 5-year graft survival of paternal recipients was better than maternal recipients (p less than 0.05). No differences were noted comparing actuarial graft survival between Blacks, Caucasians and Hispanics. 1/16 FSGS and 1/7 lupus nephritis patients had recurrence of their original disease. Posttransplant therapy in 37 patients consisted of azathioprine and prednisone while 32 patients received ciclosporin A (CSA) and prednisone. At transplantation, CSA and prednisone patients were younger, i.e., 10.7 years (range 0.5-18) compared to 13.3 years (range 4-18) and (p less than 0.03) in azathioprine and prednisone patients. The 5-year actuarial graft survival of azathioprine and prednisone patients was 57% compared to 76% in CSA and prednisone patients. 16/32 CSA and prednisone patients had their prednisone discontinued for a mean duration of 18 months (3-54 months). Ten of these 16 patients were prepubertal and had their growth hormone levels measured. All had an adequate level (greater than or equal to 10 ng/ml) poststimulation. Five of the 10 patients were less than 6 years of age and exhibited accelerated growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗