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Biomedical subjects

P Munoz

Publications and source records attributed to P Munoz.

At least 19 recordsLinked to original sources
PubMed2000

Disparity vergence double responses processed by internal error.

Disparity vergence eye movements occasionally exhibit two high-velocity components to a single step stimulus (Alvarez, T. L., Semmlow, J. L. & Yuan, W. (1998). Journal of Neurophysiology, 79, 37-44). This research investigates the neural strategy used to trigger the second component of double high-velocity vergence eye movements. Vergence doubles evoked by an experimental protocol that induces post-movement visual error were compared to doubles that occur normally. The second component of a visually evoked response double occurred later, and with slower dynamics, than that of a naturally occurring double. These differences in timing and dynamics indicate that natural double responses are mediated, at least in part, by a mechanism other than visual feedback. The faster dynamics and timing of natural doubles suggest that an internal monitoring process triggers these movements.

Adolescent↗
PubMed2000

Effects of prediction on timing and dynamics of vergence eye movements.

Periodic square waves were used to generate predictable vergence eye movement responses. The timing and dynamic characteristics of vergence eye movement responses to predictable and non-predictable stimuli were compared. Results showed significant changes in timing characteristics along with a highly characteristic anticipatory movement in the early part of predictable vergence responses. This phenomenon is similar to that seen in saccadic eye movements and appears to influence the timing and dynamics of the subsequent vergence response. A model-based analysis of dynamics showed that the pulse width, pulse gain, and step gain of the motor command signal did not show major differences between predictable and non-predictable response. However, other model parameters related to the acceleration of the response showed a substantial decrease when the movements were predictive.

Eye Movements↗
PubMed1999

Short term modification of disparity vergence eye movements.

Dynamics of disparity vergence eye movements can be modified by adaptive stimuli that generate large transient disparities. These modifications were observed for convergence as well as divergence eye movements. After modification, the peak velocities of the step responses for convergence and divergence were substantially higher than in normal baseline responses, a change observed in all four subjects studied. The change in peak velocity of a step response occurred very rapidly after presentation of the adaptive stimuli. Main sequence plots showed that first-order dynamic characteristics increased for post-adaptive responses with respect to normal step responses. Hence, response modification could be quantified as a change in gain accompanied with an increase in the effective response time constant. The adaptive responses to convergent and divergent 'disappearing' step stimuli revealed that the adaptation process modifies the high-velocity component of both disparity convergence and divergence eye movements. Moreover, a gain change in this component alone could account for both the gain and the time constant modifications seen in the overall response. A process of recovery or de-adaptation was also observed for both convergence and divergence eye movements. This observed short-term modification demonstrates a unique control mechanism for vergence eye movements that is effective in either direction.

Adaptation, Ocular↗
PubMed1999

Dynamics of the disparity vergence step response: a model-based analysis.

A new method to analyze the dynamics of vergence eye movements was developed based on a reconstruction of the presumed motor command signal. A model was used to construct equivalent motor command signals and transform an associated vergence transient response into an equivalent set of motor commands. This model represented only the motor components of the vergence system and consisted of signal generators representing the neural burst and tonic cells and a plant representing the ocular musculature and dynamics of the orbit. Through highly accurate simulations, dynamic vergence responses could be reduced to a set of five model parameters, each relating to a specific feature of the internal motor command. This dynamic analysis tool was applied to the analysis of inter-movement variability in vergence step responses. Model parameters obtained from a large number of response simulations showed that the width of the command pulse was tightly controlled while its amplitude, rising slope, and falling slope were less tightly regulated. Variation in the latter three parameters accounted for the most of the movement-to-movement variability seen in vergence step responses. Unlike version movements, pulse width did not increase with increased stimulus amplitude, although the other command signal parameters were substantially influenced by stimulus amplitude.

Computer Simulation↗
PubMed1999

Age-related changes in human ciliary muscle and lens: a magnetic resonance imaging study.

PURPOSE: To use high-resolution magnetic resonance (MR) images of the eye to directly measure the relationship between ciliary muscle contraction and lens response with advancing age. METHODS: A General Electric, 1.5-Tesla MR imager and a custom-designed eye imaging coil were used to collect high-resolution MR images from 25 subjects, 22 through 83 years of age. A nonmagnetic binocular stimulus apparatus was used to induce both relaxed accommodation (0.1 diopter [D]) and strong accommodative effort (8.0 D). Measurements of the ciliary muscle ring diameter (based on the inner apex), lens equatorial diameter, and lens thickness were derived from the MR images. RESULTS: Muscle contraction is present in all subjects and reduces only slightly with advancing age. A decrease in the diameter of the unaccommodated ciliary muscle ring was highly correlated with advancing age. Lens equatorial diameter does not correlate with age for either accommodative state. Although unaccommodated lens thickness (i.e., lens minor axis length) increases with age, the thickness of the lens under accommodative effort is only modestly age-dependent. CONCLUSIONS: Ciliary muscle contractile activity remains active in all subjects. A decrease in the unaccommodated ciliary muscle diameter, along with the previously noted increase in lens thickness (the "lens paradox"), demonstrates the greatest correlation with advancing age. These results support the theory that presbyopia is actually the loss in ability to disaccommodate due to increases in lens thickness, the inward movement of the ciliary ring, or both.

Accommodation, Ocular↗
PubMed1998

The role of radiotherapy in the conservative treatment of rectal carcinoma--the Lyon experience.

The purpose of this study was to present the Lyon experience using radiotherapy alone or with surgery, with intent to cure rectal cancer and to avoid rectal amputation. Two groups of patients were treated between 1980 and 1996: Group I with radiotherapy alone with contact x-ray for T1 N0 (101 patients) or with a combination of external beam radiation therapy (EBRT), contact x-ray and 192 iridium implant in inoperable T2-3 N0-1 patients (43 patients); Group II with preoperative EBRT either as a pilot study (158 patients) or in a randomized trial (210 patients). With contact x-ray alone it was possible to control T1 N0 in 90% of cases, and with the combined approach 70% of the inoperable patients were controlled. In Group II, anterior resection was performed in 60% to 70% of the patients. Local recurrence was seen in 11% of cases. Surgery is the basic treatment used for rectal cancer but radiotherapy is playing an increasing role in the conservative treatment of this cancer.

Adenocarcinoma↗
PubMed1997

Evidence for K+ channels involvement in capillary sensing and for bidirectionality in capillary communication.

Although the capillary sensing and communication phenomenon has been characterized, its mechanism is not clear. It has been hypothesized that capillary sensing involves a membrane potential change in the capillary endothelium and/or pericyte and that communication represents an electrotonic spread of this change along the capillary. The goal of the present study was to address this hypothesis by examining the presence of K+ channels on the capillary and by determining bidirectionality of communication. Using intravital microscopy, we locally applied K+ (100 mM), acetylcholine (ACh; 3 mM), and norepinephrine (NE; 0.3 mM) on capillaries, 400-500 microns downstream from the arteriole, at the surface of the sartorius muscle in anesthetized frogs. Responses were measured in terms of red blood cell velocity (VRBC) changes in the stimulated capillary (control prestimulation VRBC ranged from 110 to 770 microns/sec). K+ and ACh caused significant 19 and 38% increases in VRBC, while NE caused a -46% decrease, respectively. The K+ response was blocked by local pretreatment with K+ channel blocker BaCl2 (1 microM) and by pretreatment with tetraethyl ammonium chloride (TEA; 5 mM). Responses to ACh and NE were attenuated by pretreatment with 1 microM BaCl2 (to 1%) and with 50 mM TEA (to -25%), respectively. In a separate experiment, NE (3 mM) application on the capillary 500 microns away from the draining venule (capillary occluded) caused a 19% venular constriction (i.e., similar to a reported 21% arteriolar constriction caused by the NE stimulus). We concluded that (i) K+ channels were present on the capillary and (ii) capillary communication was bidirectional. We interpreted these results to be consistent with the above hypothesis of membrane potential change and electrotonic spread.

Acetylcholine↗
PubMed1995

Diagnostic value of detecting specific IgA and IgM with recombinant Trypanosoma cruzi antigens in congenital Chagas' disease.

The present study compares the early diagnosis of congenital Chagas' disease with a DOT assay using recombinant antigens with immunofluorescence antibody testing (IFAT) and an enzyme-linked immunosorbent assay (ELISA). The studies were performed using cord blood and sera of 12 infected newborns (group I) and 12 uninfected ones born to Trypanosoma cruzi-infected mothers (group II). Conventional IFAT and ELISA showed positive results for IgG at high titers, in infants and mothers of both groups; IgA antibodies were detected by ELISA in four of the infected infants and IgM was detected in two of them. All sera of the uninfected infants were negative for IgA and IgM in the ELISA. Application of a DOT assay using eight recombinant T. cruzi antigens allowed detection of specific IgA in the cord blood of six of the infected cases and IgM in eight of them. Repetition of these serologic tests in samples obtained during a monthly follow-up gave positive results for IgA in two of the initially negative infants of group I and for IgM in four of them. This means that diagnosis of congenital T. cruzi infection was confirmed, through demonstration of specific IgM, in all infected infants, and of IgA in eight of them. The importance of late detection of IgM in siblings born of infected mothers is discussed. The detection of IgM and IgA in sera obtained after birth is believed to be due to a congenital transmission of the parasite that occurred late in pregnancy. No IgA or IgM antibodies could be detected by the DOT assay in the sera of the negative controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Seasonal variation of LH and testosterone in the smallest deer, the pudu (Pudu puda molina) and its relationship to the antler cycle.

1. In order to obtain a seasonal profile of LH, three adult male pudu (Pudu puda, Molina) were sampled monthly from the saphenous vein for a period of one year. 2. A significant circannual variation of plasma LH levels was detected with an average peak value (1.77 ng/ml) recorded in February and nadir concentrations (0.19 ng/ml) observed in November. 3. The peak level of testosterone (1.54 ng/ml) was detected in March, the time of the rut.

Animals↗
PubMed1992

Short amino acid sequences derived from C1q receptor (C1q-R) show homology with the alpha chains of fibronectin and vitronectin receptors and collagen type IV.

The human C1q receptor (C1q-R) is a 65-70-kd, highly acidic, hydrophobic glycoprotein that is expressed on a wide variety of cell surfaces. Although the C1q-R itself appears to bind preferentially to C1q, the region of the ligand to which C1q-R binds is the primary binding site for several other molecules, including fibronectin, laminin, and C1q inhibitor (chondroitin 4-sulfate proteoglycan) as well as the complement C1r2C1s2 tetramer. In order to further characterize the C1q-R molecule with regard to its structure and function, highly purified C1q-R was obtained from Raji cells using DEAE-Sephacel and C1q-Sepharose CL-4B chromatography. Studies performed with 125I-labeled C1q-R demonstrated that whereas the C1q-R molecule binds poorly to a variety of human collagens including types II, III, and V, markedly enhanced binding is observed with type IV collagen and moderately enhanced binding with type I collagen. Amino acid composition studies show that the C1q-R molecule contains approximately 44% hydrophobic and 12.6% hydrophilic residues with a ratio of negatively charged to positively charged residues of about 2:1. Treatment of 125I-labeled C1q-R with endoglycosidase F lowers the apparent molecular size from 70 to 58 kd, whereas endoglycosidase H lowered the size to 64 kd. Treatment with neuraminidase, on the other hand, shifted the size of C1q-R to 60 kd. These results suggest the presence of several highly sialylated complex-type or high mannose-type N-linked oligosaccharide side chains. Because purified C1q-R has a blocked amino terminus, amino acid sequences representing internal fragments of the molecule were generated by electroblotting and in situ enzymatic digestion. When these short sequences were searched against the National Biomedical Research Foundation computer data base, a seven-amino-acid sequence, VSWQGQI, showed significant homology (100% and 80% in a five-amino-acid overlap, respectively) with the alpha chains of the human fibronectin (alpha 5 beta 1) and vitronectin (alpha v beta 3) receptors, and to a lesser degree with epidermal growth factor receptor and T cell receptor. A second sequence, ISEDNIR, showed homology with mouse collagen type IV (86% in a six-amino-acid overlap), calmodulin (60% in a seven-amino-acid overlap), and a Leishmania major surface antigen, gp63. These observations seem to predict that C1q-R has pockets of conserved sequences that are similar to those not only present in its ligand(s) but also in other cell surface receptors that may, in part, fulfill similar functions.

Amino Acid Sequence↗
PubMed1992

The 93-kilodalton protein of Borrelia burgdorferi: an immunodominant protoplasmic cylinder antigen.

Using immunoblots, we identified proteins of Borrelia burgdorferi recognized by sera from 62 patients with either acute or chronic Lyme disease. In all groups studied, the 41-kDa flagellar protein and a relatively minor 93-kDa protein (p93) were the most commonly recognized antigens in patients with acute and chronic disease due to B. burgdorferi. A murine monoclonal antibody (MAb 181.1) was developed against p93, and the antigen was detected by immunoblot analysis in four European and American strains of B. burgdorferi. On two-dimensional gel electrophoresis, p93 had an apparent pI of 6.8. Immunoelectronmicroscopy with MAb 181.1 demonstrated that p93 is located within the protoplasmic cylinder compartment of the organism. The gene encoding p93 was retrieved from a phage expression library. The derived amino acid sequence of p93 confirmed chemical characterization of the antigen, including its amino-terminal peptide sequence. The derived amino acid sequence predicted it to be predominantly alpha helical. A prominent antigenic domain located at the carboxy portion of the protein was recognized by human and rabbit polyclonal antisera and human (MAb D4) and mouse (MAb 181.1) MAbs.

Amino Acid Sequence↗
PubMed1991

Immunologic and structural characterization of the dominant 66- to 73-kDa antigens of Borrelia burgdorferi.

The 66- to 73-kDa proteins of Borrelia burgdorferi are dominant immunogens and expressed in all strains of B. burgdorferi. The humoral response to these Ag occurs relatively early during the course of infection. Two-dimensional Western blot analysis of this group of Ag revealed them to consist of a tetrad of proteins with apparent molecular mass of 66, 68, 71, and 73 kDa. Furthermore, in this study we demonstrate the 66-kDa protein to be a potent inducer of lymphoproliferation in the patient immune to B. burgdorferi. Monospecific polyclonal antibodies and mAb demonstrate that each of these proteins was immunologically distinct. However, direct amino acid sequence of the 66- and 68-kDa Ag was almost identical and had a high level of sequence similarity to the GroEL heat-shock protein (Hsp60) of Escherichia coli and the 60-kDa immunodominant protein of Treponema pallidum. The amino terminal sequence of the 71- and 73-kDa proteins of B. burgdorferi was almost identical and these proteins had remarkable sequence similarity to the DnaK heat-shock protein of E. coli (Hsp70). It appears likely, therefore, that proteins related to the heat-shock family are potent immunogens of B. burgdorferi.

Amino Acid Sequence↗
PubMed1990

Cross-antigenicity between the major surface proteins (ospA and ospB) and other proteins of Borrelia burgdorferi.

Two of the major surface Ag of Borrelia burgdorferi, the 31-kDa OspA and 34-kDa OspB proteins, are encoded by a 49-kb plasmid. In this study, mAb and monospecific polyclonal antibodies were used to define cross-antigenicity of the OspA and OspB protein to each other and to other lower molecular mass proteins by Western blot analysis. Two mAb studied, 105.5 and 184.1, were directed predominantly against the 31-kDa OspA protein. However, each also reacted with other minor bands, though with different specificities. Using V8 protease digestion and cleavage by cyanogen bromide, we demonstrated that each mAb reacted to the 31-kDa protein differently. Monospecific polyclonal rabbit and human antibodies directed against the 34-, 31-, 22-, and 20-kDa proteins were eluted from blots and used to further corroborate the cross-reactivity among these Ag. Rabbit antibodies to the 31- and 22-kDa Ag gave remarkably similar peptide maps after V8 protease digestion of the 31-kDa OspA protein, as did mAb 184.1, suggesting that this mAb recognized an immunodominant epitope common to the 22- and 31-kDa proteins. It seems likely therefore that the humoral immune response to Borrelia surface Ag may be due to a limited number of cross-reactive epitopes on distinct, but related, gene products.

Antibodies, Bacterial↗
PubMed1990

Malignant mastocytosis with circulating mast cells.

A case of malignant mastocytosis with peripheral blood involvement is presented. The course of the patient's illness was complicated by recurrent hypotensive episodes, presumed to have been caused by mast cell degranulation. Treatment with hydroxyurea was associated with persistent hypotension which resulted in death. It has been proposed that the diagnosis of mast cell leukemia be given to patients presenting with greater than 10% atypical mast cells in the blood. However, review of 16 published cases of malignant mastocytosis with circulating mast cells reveals that the clinical manifestations, complications, and survival do not vary significantly with the percentage of peripheral blood mast cells. Patients with malignant mastocytosis with significant involvement by atypical mast cells in the bone marrow and peripheral blood should be considered as having an aggressive disease, regardless of the percentage of circulating mast cells.

Biopsy↗
PubMed1989

Biochemical and immunological characterization of the surface proteins of Borrelia burgdorferi.

The immunodominant proteins and glycoproteins of Borrelia burgdorferi were analyzed by one-dimensional (1D) and 2D gel electrophoresis. More than 100 polypeptide species could be detected on silver-stained 2D gels. Separation of sonic extracts of the organism by differential centrifugation (100,000 X g) revealed several of the major proteins to reside predominantly within the pellet fraction. The antigenicity of the individual polypeptides was determined by Western (immuno-) blot analysis with sera from humans with chronic Lyme disease and from rabbits immunized with B. burgdorferi. Surface proteins of viable B. burgdorferi labeled with 125I or long-arm hydroxysuccinimide biotin were identified by gel analyses. Thirteen major surface proteins were apparent, including the highly immunogenic 41-kilodalton (kDa) endoflagellar antigen. Two of these proteins, with molecular masses of 22 and 41 kDa, were further characterized by electroblotting and microsequencing their amino termini. Significant (35%) homology between the first 20 amino acids of the 22-kDa protein and the deduced amino acid sequence of the 31-kDa (outer surface protein A) protein of B. burgdorferi may indicate that these proteins are processed similarly or are part of a gene family expressed at the surface of the organism. In addition, highly significant (88%) homology was found between the first nine amino acids of the 41-kDa protein of B. burgdorferi and the 33-kDa endoflagellar protein of Treponema pallidum, after which the sequences diverge. This observation provides in part a structural basis for the observed cross-reactivity between the two organisms and suggests alternative approaches to the development of specific immunodiagnostics.

Amino Acid Sequence↗