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Biomedical subjects

C Morales

Publications and source records attributed to C Morales.

At least 73 records · Page 4Linked to original sources

Anatomical and functional connectivity of the transected ulnar nerve after intercostal neurotization in cats.

OBJECT: Acute transfer of three intercostal nerves to the ulnar nerve was performed in cats for histological and clinical evaluation of a distal muscle reinnervation. METHODS: Infraclavicular intercostal-ulnar communications were created after dividing the motor branches of the upper intercostal nerves in 14 adult cats. Reinnervation of distal forelimb muscles in the ulnar territory was assessed by electromyographic (EMG) studies and motor function rating each month until 18 months postsurgery. In five of these treated animals, and in tour controls, horseradish peroxidase (HRP) was applied to the ulnar or intercostal nerves to study the amount and distribution of retrograde motor neuron labeling in the spinal cord. Also, samples of reinnervated muscles and neurotized ulnar nerves were processed to assess regeneration. Simple ulnar transection without reconstruction led to permanent atrophy of ulnar muscles, lack of recovery according to EMG or clinical studies, and disappearance of the ulnar motor neuron pool. In contrast, ulnar neurotization with the intercostal nerves led to a high rate of functional recovery, which began 5 months postsurgery, and progressed from muscle activity synchronized with ventilatory movements to spontaneous movements that were independent of respiration. This recovery was accompanied by substantial retrograde labeling of intercostal motor neurons after HRP application in the ulnar nerve. Cell counts showed that practically the whole motor neuron pool of the involved intercostal nerves contributed to reinnervation of the transected ulnar nerve. CONCLUSIONS: These findings demonstrate that the use of intercostal nerves to neurotize long brachial plexus nerves can achieve long-lasting and successful reinnervation of distal forelimb muscles.

Animals↗

Expression of vascular permeability factor in craniopharyngioma.

OBJECT: The expression of vascular endothelial growth/permeability factor (VEG/PF) has recently been correlated with the presence of tumor-associated cysts in some intracranial tumors. The purpose of this study was to evaluate a possible relationship between the presence of VEG/PF and the formation of cysts in craniopharyngiomas. METHODS: The expression of VEG/PF was studied in histological specimens from a series of 12 craniopharyngiomas. In this series, the tumors were classified as presenting a mainly solid pattern with small macroscopic cysts (four patients) or a mainly cystic pattern (eight patients). The mainly solid tumors containing small macroscopic cysts showed little or no VEG/PF positivity, which was mainly present in tumor cells surrounding cysts. Nevertheless, mainly cystic craniopharyngiomas showed a moderate or high degree of VEG/PF positivity in tumor cells. CONCLUSIONS: These findings indicate that the predominance of a cystic or solid macroscopic appearance of craniopharyngiomas may be influenced by the degree of VEG/PF expression within the tumor cells.

Adult↗

[Exogenous adenosine and postischemic dysfunction in the isolated rabbit heart].

It is recognized that adenosine lessens the systolic alterations of the postischemic ventricular dysfunction ("stunned myocardium"), but little is known about the drug's effects on the diastolic phase of the cardiac cycle. The aim of this work was to determine the effect of adenosine when it was administered: a) before ischemia and during reperfusion, and b) from the early reperfusion period to the end of the experiment on the systolic and diastolic function of the "stunned myocardium". An additional objective was to determine whether adenosine modifies the release of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), in the "stunned myocardium". Rabbit isolated isovolumic hearts were perfused according to Langendorff's technique, and subjected to 15 minutes global ischemia and 30 minutes reperfusion. A small latex balloon was inserted into the left ventricle via the left atrium which allowed to measure the ventricular end-diastolic pressure (diastolic stiffness) and calculate the developed pressure, the maximal rate of pressure generation and maximal rate of pressure decay (+dP/dtmax and -dP/dtmax), the ratio between these two variables (+P/-P), and the time constant of isovolumic relaxation (tau, Tau). The adenosine administered both before the ischemia period, and at the beginning of reperfusion, attenuated the systolic and diastolic stiffness alterations without modifying the isovolumic relaxation. The administration of adenosine did not diminish the CPK and LDH release significantly when it was given before the ischemia period or the beginning of reperfusion.

Adenosine↗

Iridoids from Lippia graveolens.

An investigation of the leaves of Lippia graveolens from Guatemala provided 10 iridoid and secoiridoid glucosides as well as their ester derivatives. Minor constituents were loganin, secologanin, secoxyloganin, dimethylsecologanoside, loganic acid, 8-epi-loganic acid and caryoptoside. Major constituents were the novel iridoids caryoptosidic acid and lippioside I and II consisting of caryoptosidic acid esterified at the C-6 position of glucose with p-coumaroyl or caffeoyl residues, respectively. Their structures were mainly elucidated by NMR spectroscopy.

Journal Article↗

The RNA- and DNA-binding protein TB-RBP is spatially and developmentally regulated during spermatogenesis.

Testis brain RNA-binding protein (TB-RBP) suppresses translation in vitro and attaches mRNAs to microtubules by binding to conserved elements in the 3' untranslated regions (UTRs) of specific testis and brain mRNAs. Purification of TB-RBP from testicular and brain cytoplasmic extracts has revealed that mouse TB-RBP is 99% identical to the human protein translin, a recombination "hot spot" binding protein associated with chromosomal translocations. Using a cDNA encoding TB-RBP, the gene copy number and the developmental expression of TB-RBP have been analyzed by Southern blotting, Northern blotting, and in situ hybridization. In the mouse, TB-RBP is encoded by a single copy gene. In mouse testes, three TB-RBP mRNAs of about 1.2, 1.7, and 3.0 kb are developmentally regulated with high levels of expression in meiotic and postmeiotic germ cells. A fourth TB-RBP transcript of about 3.2 kb is seen in the brain. In situ hybridization confirms high levels of testicular TB-RBP mRNAs in meiotic and postmeiotic cells, with the highest levels of TB-RBP mRNAs in pachytene spermatocytes and round spermatids of the mouse and in round spermatids of the rat. RNase H digestion assays reveal that the three TB-RBP mRNAs of mouse testes result from processing differences in their 3' untranslated regions. These data demonstrate that multiple TB-RBP mRNAs are primarily expressed in meiotic and postmeiotic germ cells in the mammalian testis, and although the specific RNA-binding ability of TB-RBP appears limited to brain and testis, TB-RBP mRNAs are widely expressed.

Animals↗

Bcl-2 slows in vitro breast cancer growth despite its antiapoptotic effect.

BACKGROUND: Although the Bcl-2 protein promotes tumor cell survival by blocking programmed cell death (apoptosis), Bcl-2 expression has been associated with favorable prognostic indicators in breast cancer. We hypothesize that despite its antiapoptotic effects, Bcl-2 slows tumor cell proliferation. MATERIALS AND METHODS: Bcl-2-negative breast cancer cells (SKBr3) were transfected with the bcl-2 gene (Bcl2-1 clone, low expression; Bcl2-2 clone, high expression) or plasmid control (Neo). Cell cycle distribution and kinetics were analyzed using bivariate flow cytometry (PI staining and pulse BrdU uptake). Cells were treated for 72 h with doxorubicin (100 ng/ml) or vehicle (0.01% DMSO) and assayed for cytosolic DNA with diphenylamine to measure apoptosis. RESULTS: Cell counting showed increased doubling time in the Bcl-2-expressing clones Bcl2-1 and Bcl2-2 (Bcl-2(+)) relative to the Bcl-2-nonexpressing lines SKBr3 and Neo (Bcl-2(-)). Cell cycle analysis showed a decreased S phase fraction in Bcl-2(+) cells. Pulse BrdU uptake showed an increased G1/G0 fraction in Bcl-2(+) cells. Doxorubicin-induced apoptosis occurred in Bcl-2(-) but not in Bcl-2(+) cell lines. CONCLUSIONS: Despite antiapoptotic effects favoring tumor survival, Bcl-2 prolongs cell cycle. Decreased tumor proliferation may account for the association of Bcl-2 expression with a favorable outcome in breast cancer, even though Bcl-2 may mediate chemoresistance in some patients.

Adenocarcinoma↗

The CarboMedics valve: experience with 1,049 implants.

BACKGROUND: The lack of valve rotatability, the structural deterioration, and the rate of valve-related complications with the standard mechanical bileaflet prosthesis led to the development of a new second-generation bileaflet valve in 1986. METHODS: Between January 1989 and March 1994, 1,049 CarboMedics valves were implanted in 859 patients. The rotatability was used in 109 mitral prostheses (21.5%) and in 61 aortic prostheses (11.6%). Follow-up was 97.1% complete, with 3,049 patient-years. RESULTS: The hospital mortality was 6.9% for the mitral group, 3.4% for the aortic group, and 10.7% for the double-valve group (p < 0.005). The actuarial survival curve at 5 years was 77.3% +/- 3.6%, 90.1% +/- 2.5%, and 79.2% +/- 3.7% (p = 0.0003), freedom from thromboembolism was 89.1% +/- 3.6%, 87.1% +/- 3.8%, and 68.8% +/- 8.2%, freedom from reoperation was 95.9% +/- 1.4%, 98.9% +/- 0.6%, and 94.9% +/- 2.4%, and freedom from valve-related complications was 68.8% +/- 4.1%, 79.5% +/- 3.5%, and 55.3% +/- 5.9% after mitral, aortic, and mitral and aortic valve replacement, respectively. There were five episodes of valve thrombosis, but no structural deterioration occurred. CONCLUSIONS: The clinical performance of the CarboMedics valve is quite satisfactory, with a low incidence of valve-related mortality and morbidity. The rotatability feature was useful when the native valve was preserved or for repeat valve replacement.

Adolescent↗

Embryology of esophageal atresia in the adriamycin rat model.

PURPOSE: The aim of this study was to describe the dysmorphogenetic process leading to esophageal atresia and tracheoesophageal fistula (EA + TEF) in the recently developed Adriamycin model of the malformation. METHODS: Time-mated pregnant rats were given either Adriamycin (1.75 mg/kg intraperitoneally) or saline on days 6 to 9 of gestation, and their embryos recovered on days 12, 12.5, and 13 were serially sectioned in the transversal plane and studied microscopically after H&E and PAS staining. The findings were compared with those of age-matched untreated embryos. RESULTS: All untreated and saline embryos were normal, whereas 49% of Adriamycin embryos had foregut malformations. Tracheoesophageal separation was complete on day 12 in control embryos, whereas 9 of 10 Adriamycin-exposed embryos had a common esophagotrachea with low emergence of the bronchi at that stage. This pattern had evolved into that of a regular EA + TEF in all nine malformed embryos by day 13. On day 12.5, esophagotrachea was found in 6 of 13 and EA + TEF in 5 of 13 embryos. Two had less well-defined malformations. CONCLUSIONS: Esophagotrachea equivalent to complete tracheoesophageal cleft is the first step leading to EA + TEF in this model. The full-blown malformation is finally acquired by partial loss of the posterior wall of the foregut, which tapers-off in the mediastinal mesenchyme and respiratory differentiation of the anterior wall down to the level of bronchial bifurcation, where it constitutes the fistula and the distal esophagus.

Abnormalities, Drug-Induced↗

Repair of nonsevere rheumatic aortic valve disease during other valvular procedures: is it safe?

OBJECTIVE: To investigate the long-term performance of aortic valve repair, we analyzed the results obtained in a 22-year period in patients who underwent repair of nonsevere rheumatic aortic valve disease during other valvular procedures. METHODS: Fifty-three patients (mean 40 +/- 11.6 years of age) with predominant rheumatic mitral valve disease had concomitant aortic valve disease in association with serious tricuspid valve disease in 25 of them. Preoperatively, aortic valve disease was considered moderate in 47.2% of the patients and mild in 52.8%. All patients underwent reparative techniques of the aortic valve (free edge unrolling, 44; subcommissural annuloplasty, 40; commissurotomy, 36) at the time of mitral or mitrotricuspid valve surgery. The completeness of follow-up during the closing interval was 100%, with a mean follow-up of 18.8 years (range 8 to 22.5 years). RESULTS: Hospital mortality rate was 7.5%. Of 49 surviving patients, 26 (53.1%) died during late follow-up. The actuarial survival curve including hospital mortality was 35.4% +/- 8.7% at 22 years. For patients who underwent mitral and aortic valve surgery, the actuarial survival curve at 22 years was 32.3% +/- 13%, whereas for patients who had a triple-valve operation the survival was 37.0% +/- 10.1% (p = 0.07). Twenty-five patients underwent an aortic prosthetic valve replacement. Actuarial free from aortic structural deterioration and valve-related complications at 22 years was 25.3% +/- 9.3% and 12.7% +/- 4.8%, respectively. CONCLUSIONS: Long-term functional results of reparative procedures of nonsevere aortic valve disease in patients with predominant rheumatic mitral valve disease have been inadequate at 22 years of follow-up. According to these data, conservative operations for rheumatic aortic valve disease do not seem appropriate.

Adolescent↗

Differences in sensitivity, maximal response and position of the concentration-response curve to methacholine between asthmatics, patients with allergic rhinitis and healthy subjects.

The aim of this study was to detect differences in maximal response and position of the concentration-response curves to methacholine between asthmatics and subjects with allergic rhinitis. A total of 228 adults (107 mild asthmatics, 96 allergic rhinitics and 25 healthy control subjects) were challenged with methacholine. The test was interrupted when FEV1 dropped by more than 40% or when the highest concentration of methacholine (200 mg ml-1) had been administered. Concentration-response curves were characterized by their PC20 (concentration of methacholine that produced 20% fall in FEV1 = airway sensitivity), and if possible, by their EC50 (concentration of methacholine that produced 50% of the maximal response = position) and level of plateau. The proportion of subjects with plateau was significantly lower in asthmatics (18.7%) than in either allergic rhinitics (57.3%) or healthy subjects (92%). It was also significantly lower in allergic rhinitics than in healthy subjects. The level of plateau for asthmatics was (means +/- SD) 31.5 +/- 5.5%, compared with 20.8 +/- 8.1% in allergic rhinitics and 13.7 +/- 6.7% in healthy subjects (P < 0.01). It was also higher in allergic rhinitics than in healthy subjects (P < 0.01). The EC50 values were decreased in asthmatics when they were compared with either allergic rhinitics or healthy subjects (geometric mean EC50: asthmatics = 2.7 mg ml-1, allergic rhinitics = 6.2 mg ml-1, healthy subjects = 8.7 mg ml-1; P < 0.01), but no significant differences were detected between allergic rhinitics and healthy subjects. These results demonstrate that in subjects with allergic rhinitis, the prevalence and level of the plateau on the methacholine concentration-response curve is intermediate between that of asthmatics and normals. Furthermore, while the asthmatic curves differ from normal in having both an increased maximal response and a leftward shift, the rhinitic curves differ only in terms of plateau level. These results suggest that airway responsiveness in asthma and allergic rhinitis may be a consequence of mechanisms that are at least partially different.

Adult↗

Peak flow variability and sputum eosinophilia in allergic rhinitis.

BACKGROUND: Although some non-asthmatic subjects with allergic rhinitis exhibit airway hyperresponsiveness and increased diurnal peak expiratory flow (PEF) variation, little is known about the critical features that determine these physiologic alterations. OBJECTIVE: In subjects with allergic rhinitis and methacholine hyperresponsiveness but no asthma symptoms, we examined whether there were features of asthmatic airway inflammation. METHODS: Forty non-asthmatic adults (11 with allergic rhinitis and methacholine hyperresponsiveness, 20 with allergic rhinitis and normal methacholine responsiveness, and 9 healthy control subjects) were studied. Sputum was induced with inhaled hypertonic saline for 5-minute periods for up to 20 minutes. Plugs from the lower respiratory tract were selected for differential counting in cytocentrifuged preparations. For the next 14 days, subjects measured their PEF two times daily. Peak expiratory flow variation was expressed as amplitude % mean. RESULTS: Peak expiratory flow variation was significantly higher in subjects with allergic rhinitis and methacholine hyperresponsiveness than in allergic rhinitis patients with normal methacholine responsiveness and healthy controls. Eosinophil counts in the induced sputum were significantly higher in the subjects with allergic rhinitis and methacholine hyperresponsiveness [median (interquartile range), 7.3 (9.0)%] compared with allergic rhinitis patients with normal methacholine responsiveness [2.5 (3.8)%, P = .03] and healthy controls [1.0 (1.0)%, P = .02]. CONCLUSION: We conclude that eosinophilic inflammation may be present in subjects with allergic rhinitis and airway hyperresponsiveness even when there are no symptoms of asthma. This could indicate that bronchial eosinophilia is insufficient to cause asthmatic symptoms.

Adult↗

Variability of peak expiratory flow rate in allergic rhinitis and mild asthma: relationship to maximal airway narrowing.

BACKGROUND: Previous studies have demonstrated a significant correlation between airway sensitivity to pharmacologic agents and daily peak expiratory flow rate (PEF) variation in asthmatic and nonasthmatic subjects. OBJECTIVE: The aim of this study was to investigate, both in patients with asthma and in subjects with allergic rhinitis, differences in daily PEF variation between subjects with plateau on the concentration-response curves to methacholine and those without plateau. METHODS: A total of 120 adults (50 with mild asthma, 52 with allergic rhinitis, and 18 healthy control subjects) were challenged with methacholine (up to 200 mg/mL) and, for the next 14 days, measured their PEF three times daily. The response to methacholine was measured by the percent decrease in FEV1. A maximal response plateau was considered if three or more of the highest concentrations fell within a 5% response range. Diurnal PEF variation was expressed as the amplitude percent mean. RESULTS: A plateau response was detected in 11 (22%) asthmatic patients, in 33 (63%) subjects with allergic rhinitis, and in 17 (94%) healthy subjects. Diurnal PEF variation was significantly greater (P < .01) in the asthmatic group without a plateau (8.8 +/- 3.7%) compared with the three groups with a plateau (asthma = 5.5 +/- 2.9%; allergic rhinitis = 4.6 +/- 2.1%; healthy = 4.7 +/- 2.3%). Those three groups with a plateau were not significantly different from each other with respect to PEF variability. Diurnal PEF variation was significantly higher in allergic rhinitis patients without plateau (7.6 +/- 3.5%) than in allergic rhinitis patients with plateau (P < .01) and healthy subjects (P < .05). The rhinitic group without a plateau, however, was not significantly different from either the asthmatic group without plateau or the asthmatic group with plateau. CONCLUSIONS: We conclude that in both asthmatic patients and subjects with allergic rhinitis, the shape of the concentration-response curve to methacholine provides new information on the relationship between airway responsiveness and PEF variability. Further, allergic rhinitis subjects without evidence of plateau have a degree of diurnal PEF variation similar to that found in patients with mild asthma. This could indicate that those subjects may have subclinical inflammatory changes in the airways.

Adolescent↗

Ovarian follicle macrophages: is follicular atresia in the immature rat a macrophage-mediated event?

Macrophages have recently been found to play roles in most ovarian events through cytokine release and/or cell-cell communication. We studied the presence of macrophages in the ovaries of neonatal (0-7 days of age), juvenile (10-20 days of age), and prepubertal (25-30 days of age) rats, as well as adult cycling rats, in relation to follicular development and atresia. Macrophages were extremely scarce in the ovarian stroma up to 30 days of age. However, at 10 days of age, about 13% of small growing healthy follicles contained macrophages among granulosa cells. The percentage of macrophage-containing follicles at 15 days of age was about 60%, and the vast majority of these follicles also had pyknotic granulosa cells, which increased in number from 15 to 20 days of age. This type of atresia showed distinctive morphological and functional features in comparison with the atretic process observed in adult cycling rats. At 25 and 30 days of age, atretic follicles in advanced stages of atresia, together with atretic follicles similar to those present in adult rats, were observed. In adult rats, only a small proportion of healthy growing follicles contained macrophages. These cells were absent from early atretic follicles, and invasion by macrophages occurred at advanced stages of atresia. These data indicate that a different type of atresia occurred during early postnatal development, probably related to the special endocrine environment in immature rats. The close association between the presence of macrophages inside the follicles and of apoptotic granulosa cells strongly supports the hypothesis that macrophages mediate follicular atresia in immature rats.

Aging↗

Macrophages, cell proliferation, and cell death in the human menstrual corpus luteum.

We studied the presence and numbers of macrophages in the different compartments of the human menstrual corpus luteum (CL) in relation to the proliferative activity and apoptosis in luteal cells. Macrophages were recognized by immunohistochemical demonstration of the lysosome-associated glycoprotein CD68, and proliferating cells by immunohistochemical detection of the cell cycle-related protein Ki67 and by counting mitotic cells. In general, changes in the number of macrophages were parallel to the functional activity of the CL. Macrophage numbers increased up to the end of the early luteal phase, remained relatively unchanged during the midluteal phase, and decreased at the late luteal phase. Furthermore, macrophages showed prominent morphological changes during the cycle. They showed round or elongated cytoplasm during the early and late luteal phases, and dendritic features in the midluteal phase. Proliferating cells were very abundant on Days 15-16 and showed a significant decrease thereafter. Most proliferating cells corresponded to stromal (mainly vascular) cells. However, about 5% of granulosa-lutein cells and about 15% of theca-lutein cells were proliferating during the early and midluteal phases. Regression of the CL at the late luteal phase was associated with both a decrease in the number of proliferating cells and an increase in the number of apoptotic cells, which were highly increased on Days 25-27 of the cycle. The number of macrophages was not related to cell proliferation nor to cell death during the luteal phase. The observed changes in both macrophage number and morphology suggest the existence of a bidirectional communication between macrophages and steroidogenic cells in the human CL, or regulation of both cell populations by similar mechanisms.

Apoptosis↗

Both prolactin and progesterone in proestrus are necessary for the induction of apoptosis in the regressing corpus luteum of the rat.

This study was conducted to analyze the roles of prolactin (PRL) and progesterone in the induction of luteal cell apoptosis and accumulation of macrophages in the regressing corpus luteum. We studied the number of apoptotic cells and macrophages in regressing corpora lutea in estrus 1) in cycling rats or after blocking PRL secretion with the dopaminergic agonist CB154, and 2) after blocking progesterone actions with the progesterone receptor antagonists RU-486 or ZK98299. Cells showing the morphological features characteristic of apoptosis contained fragmented DNA as indicated by in situ 3' end labeling. In cycling rats, a 100-fold increase in the number of apoptotic cells and a 4-fold increase in the number of macrophages was found from the evening (1600 h) of proestrus to the morning (1100 h) of estrus. Both increases were blocked by PRL suppression with CB154. Furthermore, blocking progesterone actions with progesterone receptor antagonists RU-486 or ZK98299 without affecting PRL secretion inhibited apoptosis but did not affect the accumulation of macrophages, whether treatment was started on the morning of metestrus (blocking diestrous and proestrous progesterone) or on proestrus (blocking only proestrous progesterone). Otherwise, exogenous progesterone was not effective in inducing apoptosis in the absence of PRL. These results indicate that both PRL and progesterone in proestrus are necessary for the induction of apoptosis in the regressing corpora lutea, whereas the accumulation of macrophages seemed to be dependent exclusively on the PRL surge.

Animals↗

A comparative study of mast cells and eosinophil leukocytes in the mammalian testis.

The existence of a physiological integration between the immune and endocrine systems has long been recognized. In spite of the abundant literature data on the presence of cells of the immune system in the testis, mast cells and eosinophil leukocytes have received little attention. We have studied the presence, distribution and numbers of mast cells and eosinophils in the testes of 12 mammalian species. Mast cells were frequently found in equine (stallion, ass and mule) and human testis, whereas eosinophils were nearly absent. On the contrary, eosinophils were abundant in the hare testis, while mast cells were lacking. Both cells types were present in high numbers in swine (wild and domestic boar) testis. Otherwise, mast cells and eosinophils were absent from the testicular parenchyma of several species (rat, dog, cat, bull and deer), although they were present, in most cases, around blood vessels in the tunica albuginea. The presence of high numbers of mast cells and/or eosinophil leukocytes in the testicular parenchyma of some species suggest a role for these cells in local regulatory pathways.

Animals↗