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Biomedical subjects

F Gonzalez

Publications and source records attributed to F Gonzalez.

At least 91 records · Page 5Linked to original sources
PubMed1994

Continued tumor necrosis factor receptor expression by trauma patients' monocytes (Mphi) despite TNF alpha secretion.

In investigating various mechanisms for continued elevated tumor necrosis factor alpha (TNF alpha) production in trauma patients' monocytes (Mphi), we examined TNF receptor (TNFR) levels on the patients' Mphi as a possible altered pathway leading to continued autocrine TNF alpha stimulation. Mphi TNFR synthesis and shedding are both increased as TNF alpha protein production increases. In fatal meningococcal infections, TNFR shedding fails to pace TNF alpha production. Here, isolated normal and trauma patients' Mphi (injury severity score greater than 30), were examined by flow cytometry using phycoerythrin-labeled TNF alpha to detect increased or decreased TNFR expression concomitant to Mphi production of secreted TNF alpha (as measured in the LM bioassay). Immunoaberrant patients (mitogen proliferation depressed) had reduction in detectable TNF alpha binding by their TNFR, while Mphi from immunocompetent (normal mitogen response) trauma patients' Mphi had a TNFR expression intensity comparable to normals' Mphi. Upon in vitro stimulation of TNF alpha (IFN gamma + muramyl dipeptide) normals' and immunocompetent patients' MO TNFR expression is decreased for the entire 18 h period during which secreted TNF alpha is produced, but immunoaberrant trauma patients' Mphi increased their TNFR expression, while concomitantly producing both secreted and cell-associated TNF alpha protein. Patients' Mphi with highly elevated TNF alpha levels are still expressing high levels of TNFR and capable of auto-stimulating TNF alpha production. This elevated TNFR expression could be due to reduced shedding, overproduction of TNFR, or both.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Cell responses to vertical and horizontal retinal disparities in the monkey visual cortex.

Because of the horizontal separation of both ocular globes, the projection angles are slightly different. These differences are commonly termed retinal disparities. Vertical and horizontal retinal disparities occur constantly in normal life. We have investigated the responses of single cells in cortical areas V1 and V2 of behaving Macaca mulatta monkeys to retinal disparities by using dynamic random dot stereograms. Our findings show that cortical visual cells are sensitive to both vertical and horizontal disparities. To calculate the distance between two objects in a three-dimensional space from horizontal disparities, it is necessary to know the fixation distance. It has been suggested that the horizontal gradient of vertical disparity contains information to estimate the fixation distance and therefore to scale horizontal disparities. We suggest that these cells sensitive to horizontal and vertical disparities represent a neural mechanism that provides information to the visual system in order to achieve a correct eye alignment and depth perception.

Animals↗
PubMed1993

Stable expression of human cytochrome P450 1A1 cDNA in V79 Chinese hamster cells and metabolic activation of benzo[a]pyrene.

A V79 Chinese hamster cell line stably expressing human cytochrome P450 1A1 (CYP1A1) was obtained by chromosomal integration of the human CYP1A1 cDNA under the control of the SV40 early promoter. Chromosomal integration was verified by Southern analysis, and effective transcription of the human CYP1A1 cDNA was demonstrated by Northern analysis. The CYP1A1 cDNA-encoded protein was characterized by Western analysis using anti-rat CYP1A1. Intracellular association of CYP1A1 with the endoplasmic reticulum could be visualized by in situ immunofluorescence. Crude cell lysates of the V79 derived cell line was able to catalyze 7-ethoxyresorufin-O-deethylation (EROD) with an activity of about 50 pmol min-1 mg-1 total protein, and an aryl hydrocarbon hydroxylase activity (AHH) of 25 pmol min-1 mg-1. CYP1A1 dependent cytotoxicity, measured by neutral red uptake, and genotoxicity, determined by the frequency of micronucleus formation, of benzo[a]pyrene (B[a]P) and trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-7,8-diol) could be demonstrated at substrate concentrations as low as 10 nM. Thus, this cell line presents a sensitive tool for studying CYP1A1 mediated metabolism of polycyclic aromatic hydrocarbons (PAH). B[a]P and the purified (+)- and (-)-enantiomers of B[a]P-7,8-diol were compared for their mutagenicity. The (-)-enantiomer was found to be 3-5-fold more mutagenic than the (+)-enantiomer.

Animals↗
PubMed1993

Cross-reactivity of thirteen monoclonal antibodies with ten vaccinia cDNA expressed rat, mouse and human cytochrome P450s.

Twelve monoclonal antibodies (MAbs) to rat cytochrome P450s and one MAb to a scup (fish) P450 have been isolated, characterized, and are currently in common use. Expression of cDNAs for different P450s from a vaccinia vector offers a rapid and simple way toward the production of individual P450s. The thirteen MAbs were examined for their cross-reactivity with ten cDNA expressed human, rat, and mouse P450s. Three MAbs to rat 1A1 and fish 1A1 cross-reacted with cDNA expressed mouse 1A1. One of the latter MAbs, 1-7-1 but none of the others cross-reacted with mouse 1A2. Surprisingly, the fish MAb to 1A1 also cross-reacted with human 2E1. Two MAbs to rat 2B1/2B2 cross-reacted with rat 2A1. An MAb to rat 2C11 cross-reacted with human 2C9. Two MAbs to rat 2E1 cross-reacted with human 2E1. Finally, two MAbs to rat 3A1 cross-reacted strongly with human 3A4. These studies open the door to constructing a library of MAbs with defined binding activity to the P450s of human and other species.

Animals↗
PubMed1993

Endogenous generation and presentation of the ovalbumin peptide/Kb complex to T cells.

Peptide fragments are displayed on the APC surface by MHC class I molecules as ligands for appropriate TCR. Sequence analysis of MHC-bound peptide mixtures has suggested that naturally processed peptides are defined by their length and by the presence of MHC allele-defined consensus motifs. To define the minimal OVA peptide presented by Kb MHC, and the requirements for generation of endogenous OVA/Kb complex, APC were transfected with OVA cDNA constructs. We show that optimal stimulation of OVA/Kb-specific B3Z T cell hybrid by Kb-APC requires the OVA257-264 peptide (SIINFEKL, SL8) whether added exogenously, or when synthesized endogenously as precursor polypeptides. Thus, all information necessary for expression of the OVA/Kb complex is contained within the Kb octapeptide motif shared by SL8. Unexpectedly, the SL8/Kb or the influenza NP/Db complexes were also generated in APC even when the peptide coding sequences were placed in incorrect translational reading frames. By contrast, identical manipulations of the translational reading frame of the lacZ reporter gene reduced protein synthesis to undetectable levels demonstrating the remarkable efficiency with which endogenous peptide/MHC are generated in and presented by APC to T cells. These characteristics of the endogenous presentation may explain how large numbers of distinct peptide/MHC complexes are displayed on the cell surface and surveyed by TCR.

Amino Acid Sequence↗
PubMed1993

Neurons located in the trigeminal sensory complex and the lateral pontine tegmentum project to the oculomotor nucleus in the rabbit.

Neurons located in the trigeminal sensory complex (TSC) and the lateral pontine tegmentum (LPT) have been reported to project to both the accessory abducens and the facial nuclei, which innervate the retractor bulbi and orbicularis oculi muscles respectively, in order to control the nictitating membrane (NM) and eyelid defensive reflex. Since muscles innervated by the oculomotor nucleus (OCM) also appear to be involved in this reflex, retrograde and anterograde tracers were used in this study to determine whether there are projections from the TSC and LPT to the OCM in the rabbit. Injections of horseradish peroxidase (HRP) in the OCM nucleus labeled neurons in the LPT surrounding the trigeminal motor nucleus dorsally, laterally and ventrally. Only a few scattered neurons were found in the principal and spinal trigeminal nuclei. Injection of biocytin in the LPT area containing most of the HRP-labeled neurons caused anterograde labeling of fibers that crossed the midline and ascended just dorsal to the contralateral medial lemniscus. A proportion of these fibers coursed in a dorsal direction to enter and terminate within the OCM contralateral to the injection site. The location of the motoneuronal groups innervating the different extraocular muscles was studied by retrograde transport of HRP, and compared with the distribution of biocytin-labeled terminals. It was found that the terminals were located in the superior rectus and the levator palpebrae zone of the nucleus. We discuss the functional significance of this projection for the eyelid and NM response.

Animals↗
PubMed1993

Orientational influences of layer V of visual area 18 upon cells in layer V of area 17 in the cat cortex.

We examined the orientation tuning curves of 86 cells located in layer V of area 17, before, during, and after focal blockade of a small (300-microns diameter) region of near-retinotopic register in layer V of area 18 of quantitatively established orientation preference. Such focal blockade revealed three distinct populations of area 17 layer V cells-cells with decreased responses to stimuli of some orientations (21%), cells with increased responses to stimuli of some orientations (43%), and cells unaffected by the focal blockade (36%). These effects were clearcut, reproducible, and generally directly related to the known receptive field properties of the cell recorded in area 18 at the center of the zone of blockade. These effects were also analyzed in terms of alterations in orientation bandwidth in the cells in area 17 as a result of the blockade-bandwidth increases (22%) and decreases (24%) were found; however, these changes were essentially unrelated to the measured receptive field properties. Inhibitory and excitatory effects were most pronounced when the regions in areas 17 and 18 were of like ocular dominance and were of similar orientation preference. Inhibitory effects (suggesting a normally excitatory input) were most dependent upon the similarity of receptive fields; excitatory effects (suggesting a normally inhibitory input) were less heavily dependent.

Animals↗
PubMed1993

Influence of layer V of area 18 of the cat visual cortex on responses of cells in layer V of area 17 to stimuli of high velocity.

Focal blockade of restricted regions in layer V of area 18 was used to assess the contribution of this region to the responses to high-velocity stimuli of cells in retinotopically matched, layer V in area 17. In 40% of cases, blockade within area 18 revealed responses of area 17 cells to high-velocity stimuli to which they previously showed only poor responses. Stimulus specificity of the cells in area 17 was otherwise unaltered. All effects were reversible and repeatable. We suggest that a component of the output of layer V from area 18 normally suppresses the responses of retinotopically matched cells within area 17 to stimuli of high velocity, thereby enhancing the specificity of those cells to stimuli of low velocity.

Animals↗
PubMed1993

Binocular matching in monkey visual cortex: single cell responses to correlated and uncorrelated dynamic random dot stereograms.

This paper presents results obtained from experiments performed on two behaving monkeys (Macaca mulatta) viewing correlated and uncorrelated dynamic random dot stereograms. Extracellular single unit activity was recorded from areas V1 and V2. We found that cells sensitive to correlated stereograms (38%) were also sensitive to uncorrelated stereograms. Regarding their response to both situations, these cells were grouped into two types. The first type (57%), termed "correlation-sensitive cells", responded with statistically significant difference to correlated and uncorrelated stereograms. The second type responded equally to both stereograms (43%), and therefore they were termed "correlation-insensitive cells". Our data suggest that these two types may form two populations with different functions subserving depth perception.

Animals↗
PubMed1993

Radial and ulnar artery repairs: assessing patency rates with color Doppler ultrasonographic imaging.

This study was undertaken to evaluate the patency rate of radial and ulnar artery repairs performed with use of the magnification afforded by the operative microscope. Color Doppler ultrasonographic imaging was chosen as a reproducible, noninvasive technique to evaluate patency and graphically display vascular flow characteristics. Twenty-eight consecutive patients with 35 arterial injuries form the study group. Twenty-four patients with 31 arterial lacerations were available for enrollment in the protocol. Follow-up ranged from 1 to 40 months (average, 10 months). Eighteen male and six female patients sustained 13 radial and 18 ulnar artery lacerations, all sharp. Four patients required interposition vein grafting. Overall patency after repair was found to be 84%, with 82% of single vessels and 86% of double vessels patent. The patency of single vessels repaired without the use of vein grafts was 100%. These results indicate that microscope-assisted repairs of the radial and ulnar arteries remain patent at a higher rate than is commonly cited.

Color↗
PubMed1993

Intravenous disodium etidronate therapy in spinal cord injury patients with heterotopic ossification.

The goal of the present study was to use intravenous etidronate in the acute phase of heterotopic ossification (HO) in an attempt to achieve a high initial drug concentration at the site of the active ectopic ossification. The study included 27 consecutive patients with an acute onset of HO after spinal cord injury (SCI). The three-phase bone scan was used to confirm clinical diagnosis of HO. Disodium etidronate (Didronel) 300 mg was administered intravenously daily for 3 to 5 days. In 20 patients there was a rapid (1-2 days) decrease of soft tissue swelling (p < 0.01) with no side effects associated with the intravenous administration. In seven patients there was minimal or no improvement of edema after intravenous etidronate. In these patients deep vein thrombosis was found in the affected limbs. The effect of high dose etidronate on HO was determined in the group of 13 patients with positive clinical and scintigraphic finding of an acute HO, but negative radiographic studies. After intravenous administration of etidronate for 3 days (300 mg/day) the drug was continued orally with 20 mg/kg/day for 6 months. A placebo was not used in this study. In eight patients there was no radiographic evidence of HO after therapy while two patients had minimal ossifications. In three patients therapy was interrupted and all developed HO in 1-2 months.

Administration, Oral↗
PubMed1993

Reduction mammaplasty improves symptoms of macromastia.

The condition macromastia has not been defined and characterized precisely by the medical community. Whether the patient with hypertrophic breasts is a candidate for or can be helped by reduction mammaplasty is unclear to both the medical and the lay community. A prospective study of 39 women undergoing reduction mammaplasty surgery was initiated to answer these questions. Patients rated the severity of their somatic pain symptoms and discomfort before reduction mammaplasty and again after complete recovery. The severity of their symptoms and complaints was numerically graded and analyzed. These data were compared with similar data obtained from 40 "small-breasted" women of similar age. Headache, neck pain, back pain, shoulder pain, and bra strap groove pain were present in 60 to 92 percent of patients, and 97 percent of patients had at least three of these pain symptoms preoperatively. All the patients had reduction of their pain symptomatology postoperative, and 25 percent of the study patients had total elimination of pain symptoms by reduction mammaplasty. The postoperative incidence and severity of pain symptoms and discomfort complaints were statistically equivalent to or less than the levels in the control group.

Adult↗
PubMed1993

Unintentional intraocular injection of corticosteroids.

In this report we present a patient on whom a sub-Tenon injection of steroids was performed, with the intention of treating an active chorio-retinitis threatening the macula. The globe was inadvertently penetrated and part of the steroid solution released into the vitreous cavity. Conservative treatment was decided upon and a spontaneous complete resolution of the complication was observed after a period of 24 days.

Anti-Inflammatory Agents↗
PubMed1993

Preoperative and postoperative nipple-areola sensibility in patients undergoing reduction mammaplasty.

Objective data on nipple and areola sensibility are scarce. For women with macromastia, there is little published information available indicating the incidence and intensity of postoperative nipple and areola sensibility. This prospective study was undertaken to evaluate nipple and areola sensibility in "small-breasted" control subjects as well as in patients with macromastia before and after reduction mammaplasty. Preoperative and postoperative Semmes-Weinstein pressure threshold testing was performed on 84 breasts in 43 patients and on 12 breasts of A or B cup size in the control group. The patients underwent reduction mammaplasty by the central parenchymal pedicle technique or the laterally based inferior pedicle technique. Nipple-areola sensibility was retained in 96 percent of breasts when the excision of breast tissue was less than 550 gm and 85 percent of breasts when the excision was greater than 550 gm. Overall, nipple-areola sensibility was retained in 90.5 percent of the 84 breasts tested. In those breasts in which nipple-areola sensibility was retained after surgery, there was no statistical difference in the preoperative and postoperative Semmes-Weinstein pressure threshold values. When pressure threshold values were compared in patients who had less than 550 gm of tissue resected, patients who had greater than 550 gm of tissue resected, and controls who had not undergone surgery, the trend of decreasing nipple-areola sensibility with increasing breast size was clearly seen.

Female↗
PubMed1992

Urokinase combination chemotherapy in small cell lung cancer. A phase II study.

BACKGROUND AND METHODS: Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year. RESULTS: In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient. CONCLUSIONS: These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.

Actuarial Analysis↗
PubMed1992

Genetically engineered V79 Chinese hamster cells for stable expression of human cytochrome P450IA2.

V79 Chinese hamster cells were genetically engineered for stable expression of human P450IA2. Full length cDNA, encoding human P450IA2, was inserted into an SV40 early promoter containing eukaryotic expression vector and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to the neomycin derivative G418) into V79 Chinese hamster cells. The recombinant expression vector was introduced into two different V79 sublines, one expressing an endogenous acetyltransferase (V79-NH), the other not (V79-MZ). The presence of human cytochrome CYP1A2 cDNA in the G418 resistant V79 cell clones was confirmed by Southern blotting. The transcription of the cDNA into mRNA was detected by Northern blotting and the translation into an authentic cytochrome P450IA2 protein was shown by Western blotting. The enzymatic activity in these cells was determined by the cytochrome P450IA2-dependent methoxy-, ethoxy-, benzoxy-, and pentoxyresorufin dealkylation activity.

Animals↗
PubMed1992

Anteroposterior shift in rigid and soft implants supported by the intraocular capsular bag.

We compared the depth of the anterior chamber and the optimal distance refraction in a group of patients with soft and rigid intraocular implants under pilocarpine (maximal ciliary contraction) and cyclopentolate (maximal ciliary relaxation) in order to determine if lens movement might account for the apparent accommodation phenomenon. Lens shifts ranging from 1.5 to 0.02 mm and refractive variations up to 1 D were found. However, the discrepancies between amount of shift and refractive variations suggest that lens movement does not play a relevant role in this phenomenon.

Accommodation, Ocular↗