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Biomedical subjects

A Rodriguez

Publications and source records attributed to A Rodriguez.

At least 109 records · Page 6Linked to original sources

Aromatase activity and estradiol in human breast cancer: its relationship to estradiol and epidermal growth factor receptors and to tumor-node-metastasis staging.

PURPOSE: The present report attempts to clarify whether there is a relationship between aromatase activity (ARAC) and estradiol (E2), hormonal receptors, E2 receptor (ER), and epidermal growth factor receptor (EGFR), as well as with tumor stage and histopathology in human breast cancers. MATERIALS AND METHODS: We studied 225 breast carcinomas, 67 of which were premenopausal and 158 postmenopausal. In each sample, ARAC, EGFR, ER, and E2 were quantified. ARAC was quantified by Thompson and Siiterii's method, EGFR was quantified with a two-point assay method using radioactive iodine (125I)-EGF as ligand, and ER was measured by the Scatchard method using 3H-E2. E2 was quantified by radioimmunoassay in the diethylether tumor extract. RESULTS: ARAC was found in 64% of the cancers studied. There is a strong direct association between ARAC and tumor size in postmenopausal patients (P = .001). In the postmenopausal group, the proportion of ARAC-positive (ARAC+) tumors is significantly higher among ER-positive (ER+) than ER-negative (ER-) ones (P less than .001). ER+ tumors also have significantly higher levels of E2 than do ER- ones (P less than .0001); similarly, ARAC+ tumors have significantly higher levels of E2 than do ARAC- ones (P less than .0001). There is a significant multiple linear correlation between the log of the levels of ARAC, ER, and EGFR and the log of tumor E2 (P less than .0001). The correlation coefficients obtained show that ARAC and ER have a positive effect on tumor E2. CONCLUSION: The results obtained suggest the importance of tumor ARAC in the tumoral levels of E2 and reinforce the possible biologic significance of tumor ARAC, especially in postmenopausal breast carcinoma patients.

Adult

Suppressive effect of tetrahydrocannabinol on specific T cell subpopulations in the thymus.

The effects of THC (delta-9-tetrahydrocannabinol) on thymocytes from adult BALB/c mice were investigated following in vitro stimulation with the T cell mitogen Concanavalin A (Con A). Con A treatment resulted in a decrease in the relative percent of L3T4+/Ly2+ cells (double positive; immature) with a concomitant increase in the percent of Ly2 cells (suppressor/cytotoxic). No change in the percent of L3T4 cells (helper) occurred. In addition, Con A stimulation resulted in an increase in the absolute number of Ly2 cells, with no change in number of L3T4 cells. Stimulation with the mitogen led to an increase in fluorescence intensity (indicative of relative number of markers) of Ly2 markers on Ly2 single positive cells as well as on L3T4+/Ly2+ cells. There was a moderate mitogen induced increase of L3T4 markers, but only on L3T4 single positive cells. Exposure to THC resulted in a definitive suppressive effect on Con A induced thymus cell proliferation. The suppression was primarily evidenced in the single positive Ly2 subpopulations. Since the thymus is the source of immunocompetent lymphocytes to the secondary lymphoid organs, it seems plausible that marijuana negatively affects maturation of these cells in the developing individual.

Animals

The RBE-LET relationship for rodent intestinal crypt cell survival, testes weight loss, and multicellular spheroid cell survival after heavy-ion irradiation.

This report presents data for survival of mouse intestinal crypt cells, mouse testes weight loss as an indicator of survival of spermatogonial stem cells, and survival of rat 9L spheroid cells after irradiation in the plateau region of unmodified particle beams ranging in mass from 4He to 139La. The LET values range from 1.6 to 953 keV/microns. These studies examine the RBE-LET relationship for two normal tissues and for an in vitro tissue model, multicellular spheroids. When the RBE values are plotted as a function of LET, the resulting curve is characterized by a region in which RBE increases with LET, a peak RBE at an LET value of 100 keV/microns, and a region of decreasing RBE at LETs greater than 100 keV/microns. Inactivation cross sections (sigma) for these three biological systems have been calculated from the exponential terminal slope of the dose-response relationship for each ion. For this determination the dose is expressed as particle fluence and the parameter sigma indicates effect per particle. A plot of sigma versus LET shows that the curve for testes weight loss is shifted to the left, indicating greater radiosensitivity at lower LETs than for crypt cell and spheroid cell survival. The curves for cross section versus LET for all three model systems show similar characteristics with a relatively linear portion below 100 keV/microns and a region of lessened slope in the LET range above 100 keV/microns for testes and spheroids. The data indicate that the effectiveness per particle increases as a function of LET and, to a limited extent, Z, at LET values greater than 100 keV/microns. Previously published results for spread Bragg peaks are also summarized, and they suggest that RBE is dependent on both the LET and the Z of the particle.

Animals

Influences of witnessed affect on information processing in children.

Children between the ages of 5 and 10 years watched a videotape of a child having a routine medical exam. Embedded within the scenes were systematic variations of depicted facial affect shown by doctor and child. Measures were taken of autonomic reactions and information-processing errors in response to positive, neutral, and negative affective cues. For 5-6-year-olds, processing errors were greatest in the negative affect condition. Additionally, peak increases in heart rate (HR) and skin conductance level (SCL) were demonstrated by 5-6-year-olds in response to negative affect shown by the witnessed child; increases in HR were in turn predictive of processing errors. Older children (9-10 years) showed trends reflecting reduced processing errors in response to witnessed negative affect. It was suggested that younger children respond to salient threat cues with a "defensive" response pattern that is relatively adaptive at younger but not older ages.

Affect

Retroperitoneal hematoma after blunt trauma.

We reviewed retrospectively 233 consecutive patients with retroperitoneal hematoma (RPH) resulting from blunt trauma. This study group represented 2.9 per cent of all admissions for blunt trauma and 13 per cent of all admissions for blunt abdominal trauma. Motor vehicle accidents predominated as the cause of injury. Fifty-five per cent of the patients had fractures of the pelvis. Laparotomy was the primary method used in diagnosing RPH (73 per cent). The RPH was located in zone I in 14 per cent of patients, zone II in 37 per cent, zone III in 46 per cent and zone IV in 3 per cent. The RPH was explored in 35 per cent of all patients. Major vessels were the most common organ system injured (21 per cent) in patients with zone I RPH. The kidney was the most commonly injured organ (27 per cent) in patients with zone II RPH. Injury of either the pancreas or duodenum in 14 per cent of patients with right-sided zone II RPH indicates the need for careful evaluation of those organs at operation. Patients with zone III RPH associated with fractures of the pelvis should be explored only rarely--when main iliac vascular injury is suspected (4.6 per cent in this series). Otherwise, a systematic approach using external fixator devices and angiographic embolization should be used. The over-all morbidity and mortality rates of 59 and 39 per cent, respectively, emphasize the need for aggressive resuscitation, rapid control of hemorrhage and a multidisciplinary approach to the management of these patients.

Abdominal Injuries

Injuries of the abdominal aorta from blunt trauma.

Blunt injuries of the abdominal aorta are rarely reported in the literature. If left undiagnosed, these injuries may have catastrophic consequences. Four patients with blunt abdominal aortic lesions, identified in the authors' trauma registry, are presented in this report, along with a discussion of the pertinent literature to illustrate clinical management techniques. The mechanisms of injury include motor vehicular crashes (most frequent) with or without seatbelt use, abdominal blows, falls, and abdominal crush injuries. The spectrum of aortic lesions ranges from simple contusion or intramural hematoma to intimal disruption, false aneurysm, or frank rupture. Aortography should be performed in all stable patients with suspected aortic injury. All central-medial retroperitoneal hematomas discovered at laparotomy for blunt trauma should be explored after proximal and distal control of the aorta is obtained. Strict adherence to these principles, maintenance of standard vascular technique, and aggressive, expeditious resuscitative evaluation may improve survival.

Adult

Priorities and diagnostic studies in the management of the injured patient.

The traumatized patient is best served by an orderly and sequential resuscitation and evaluation. Primary priorities include the establishment of a secure airway, adequate ventilation and hemodynamic status. These considerations should be followed by a brief history, systemic physical examination and radiographic studies. Studies utilized in blunt trauma include diagnostic peritoneal lavage and computed tomography. Nuclear magnetic resonance and ultrasound may prove useful in the future. In penetrating trauma, traversing missiles mandate surgical exploration. Stab wounds may be managed by several alternative methods. Emergency thoracotomy has a limited role in the blunt trauma patient but may be life saving in those suffering penetrating trauma.

Emergency Medical Services

Pre-existing disease in trauma patients: a predictor of fate independent of age and injury severity score.

Improvement in trauma management requires a better understanding of the effect of a patient's preinjury health status on outcome. Specific historical findings and laboratory criteria were used to define pre-existing disease (PED) states and determine if they were independent predictors of fate in trauma victims. Of 7,798 adult patients admitted to a level I trauma center from July 1986 through June 1990, 16.0% (1,246) had greater than or equal to 1 PED. The PED+ and PED- patients had no significant difference in Injury Severity Scores (ISSs) (15.7 versus 15.6) and admission Glasgow Coma Scale (GCS) scores (13.9 versus 13.8). The PED+ patients were older (49.2 versus 30.6 years) (p less than 0.001) and had a higher mortality rate (9.2% versus 3.2%) (p less than 0.001) than PED- patients. Mortality rates were also elevated for patients with greater than or equal to 2 PEDs (18%) and for those with renal disease (38%), malignancy (20%), and cardiac disease (18%) (p less than 0.001) compared with PED- patients. Controlling for age and ISS, there was an association between PED and mortality (Mantel-Haenszel p less than 0.03). Multivariate regression showed that PED is an independent predictor of mortality (R2 = 0.1918; p less than 0.0001). The greatest increases in mortality were found among patients less than 55 years and with ISS less than 20. Changes in prehospital triage criteria and outcome scoring are needed. Improvements in the management of trauma victims with chronic disease may decrease their mortality rate.

Adult

cAMP stimulates cholesteryl ester clearance to high density lipoproteins in J7774 macrophages.

The regulation by cAMP of cholesteryl ester hydrolysis and net depletion of cellular cholesteryl ester (cholesteryl ester clearance) in J774 murine macrophages was explored. Using Sandoz 58035 to selectively inhibit acyl CoA:cholesterol acyltransferase, we showed that the absolute rate of cholesteryl ester hydrolysis was stimulated 2-fold in J774 cells by the cAMP analogues 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate and dibutyryl-cAMP. The rate of hydrolysis was also stimulated by prostaglandin E1, by cholera toxin, and by a mixture of forskolin and isobutylmethylxanthine, but was not affected by epinephrine or dibutyryl-cGMP. These data demonstrate that cholesteryl ester hydrolysis in J774 cells can be stimulated by cAMP-dependent protein kinase. Cholesteryl ester clearance from J774 cells was achieved upon incubation with high density lipoproteins (HDL) plus CPT-cAMP but not with HDL alone. HDL-mediated cholesteryl ester clearance was dependent on the concentration of both HDL and CPT-cAMP. The data suggest that the defect responsible for the lack of HDL-mediated cholesteryl ester clearance in J774 cells involves a failure to modulate cAMP levels.

Animals

New horizons in management of hypothermia and frostbite injury.

Diagnosing hypothermia requires a high index of suspicion. Restoring lost heat with careful attention to hemodynamics usually results in complete recovery. Frostbite is best treated by physicians who are cognizant of the pathophysiology of cold injury. Although alternative methods of intervention are being tested, rapid rewarming and anti-inflammatory agents are integral to treatment protocols.

Accidents

Congenital absence of the nose and nasal fossae.

We describe a case of complete nasal agenesis and absence of the nasal fossae, without alterations in the central nervous system. The physical and intellectual development of the infant to date has been absolutely normal. Opening of the nasal respiratory passage was not required in our patient as he did not show respiratory problems during deglutition. - Microphthalmia in the right eye with iridoretinal coloboma and right cryptorchidism were also noted. When the child was 9 months old a right orbital asymmetry became evident due to a growth deficit of the microphthalmic eye. This improved after placement of an expandable prosthesis in the orbit to stimulate its growth. - When the child is 4 years old, he will start to use a nasal prosthesis supported by implantology. Final reconstruction of the nasal pyramid will take place after he is 15 years of age.

Child, Preschool

The role of cyclic nucleotide mediators in latency and reactivation of HSV-1 infected neuroblastoma cells.

The mechanisms that control herpes simplex virus type 1 latency and reactivation are still poorly understood. We developed an in vitro murine neuroblastoma cell HSV-infected, acyclovir suppressed model to study the influence of different cyclic nucleotide mediators on the latency and reactivation of HSV-1. A positive cDNA 'in situ' hybridisation for HSV genome was used to prove the establishment of a viral-host cell nuclear relationship. An ABC-immunoperoxidase reaction to cell surface HSV mature glycoproteins was also performed to determine the time of viral reactivation with formation of mature virions. Supernates of cultured cells were placed on Vero cells for confirmation of reactivation by classic cytopathic effect. Theophylline (50 micrograms/ml) and dibutyryl-cAMP (0.1, 0.5, 1 mg/ml) produced the most pronounced response, accelerating HSV reactivation time by 150%. Epinephrine (10, 20 micrograms/ml) had an intermediate effect on accelerating viral reactivation; and verapamil (20, 50 micrograms/ml), theophylline and epinephrine at lower doses had a smaller effect. Carbamylcholine (10 micrograms/ml) prolonged the time to viral reactivation by 100%, 36 hours compared to control time of 18 hours. Insulin (0.1, 0.5, 1 mg/ml) also prolonged HSV 'latency' by six hours. Exogenous dibutyryl-cGMP and carbamylcholine at lower concentrations did not have an effect on viral reactivation. These findings suggest that there is a relationship between changes of intracellular concentration of cyclic nucleotides and HSV latency and reactivation.

Animals

Immunomagnetic bead isolation of megakaryocytes from guinea-pig bone marrow: effect of recombinant interleukin-6 on size, ploidy and cytoplasmic fragmentation.

Guinea-pig bone marrow megakaryocytes were isolated using an antibody to platelet glycoprotein Ib and a second antibody conjugated to magnetic beads. The procedure yielded an average of 644,800 megakaryocytes from two guinea-pigs with an average viability of 83%. All of the platelet glycoprotein Ib positive cells also expressed the platelet glycoprotein IIb-IIIa complex. The size and ploidy of megakaryocytes isolated by this technique were analysed in the presence of 10 ng/ml of interleukin-6 (IL-6). Without IL-6 megakaryocyte size increased significantly after 24 h, but an even larger increase in size occurred in the presence of IL-6. The modal ploidy class was 16N with an average of 19% 2N, 2.6% 4N, 16.4% 8N, 50.8% 16N and 11.1% 32N cells as determined by flow cytometry. Measurements made by microspectrophotometry were in close agreement. After 24 h incubation there was a significant rise in the percentage of 2N and 32N cells. The ploidy distribution after 24 h with IL-6 was the same as the control. Megakaryocytes cultured in the absence of serum on collagen gels did not form pseudopods and fragment, as occurs with serum (Leven et al, 1987). Addition of IL-6 to the serum-free cultures caused megakaryocytes to form extensive proplatelet extensions. We conclude that large numbers of pure guinea-pig bone marrow megakaryocytes can be isolated by immunomagnetic bead selection, including low ploidy immature megakaryocytes. Spontaneous maturation occurred as evidenced by the increase in megakaryocyte size and ploidy. IL-6 altered megakaryocyte size and morphology but not ploidy, indicating that these different characteristics of megakaryocytes may be regulated separately.

Animals

Growth progression and 24-hour hormone profile in an infant treated chronically with a long-acting somatostatin derivative.

The diagnosis of nesidioblastosis was established in a 9-month-old male child with a history of recurrent convulsive seizures and hypoglycemia. After unsuccessful subtotal pancreatectomy, treatment was started with the long-acting somatostatin derivative Sandostatin (Octreotide, Sandoz) at a dosage of 25 micrograms t.i.d. spaced between carbohydrate-enriched meals. With this regime, blood glucose was maintained at the low normal range and seizures ceased. During a 30-month observation period, growth velocity and weight progression were well within the predicted limits. A 24-hour hormone profile recorded at the end of the observation period revealed the following: (1) failure to improve blood glucose with carbohydrate-enriched food due to reactive hyperinsulinemia; (2) hyperglycemic reaction after administration of Sandostatin caused by a reduction of plasma insulin; this effect was particularly marked during sleep; (3) low mean GH, decreased spiking frequency and reduced area covered by the nocturnal peaks by recognized standards, and (4) normal somatomedin C levels for age. Interpretation of growth hormone (GH) data is hindered by the lack of pertinent information from the patient's age group. Recording of normal growth progression in the case illustrated here can only be explained by the capability of a reduced GH secretory rate to maintain full biological activity as shown by the normal plasma level of somatomedin C. Indeed, recent evidence has been provided elsewhere for normal growth progression in the presence of low GH secretion, although other factors unrelated to this hormone may also be operative at this early age. Further reports concerning the treatment of non-GH-dependent conditions with somatostatin derivatives will certainly contribute to the better understanding of the mechanisms governing growth in the postnatal period.

Blood Glucose