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Biomedical subjects

M Baca

Publications and source records attributed to M Baca.

31 records · Page 2Linked to original sources
PubMed1995

Depressed T-cell proliferation associated with susceptibility to experimental Taenia crassiceps infection.

Peritoneal infection with Taenia crassiceps cysticerci of naturally resistant (C57BL/10J and C57BL/6J) and susceptible (BALB/cAnN) mice induces a cellular immune depression. T-cell proliferation in response to concanavalin A (ConA) or anti-CD3 was significantly depressed in infected mice of all strains tested. However, in resistant mice, the diminished response to ConA was transient and animals recovered normal responsiveness at day 40, whereas susceptible mice remained suppressed throughout the 40 days of the experiment. In contrast, the proliferative response to anti-CD3 was lower in infected mice than in noninfected controls regardless of differences in natural susceptibility of the strains. Intraperitoneal injection of mice with a parasite extract also induced a depression of the response to ConA, although not as strong as that produced by the parasite itself. This depression is not due to direct effects by parasite antigens over host lymphocytes, as proliferation is not affected by the presence of cysticercal antigens added in vitro. Diminished interleukin-2 production during the parasitosis accounts at least in part for the diminished responses to ConA. A primary infection favors parasite establishment after a second challenge, pointing to the relevance of the immunodepression in generating a host environment favorable to the parasite.

Animals↗
PubMed1994

Complete chemical structure of photoactive yellow protein: novel thioester-linked 4-hydroxycinnamyl chromophore and photocycle chemistry.

The unique ability of photoactive proteins to capture and use energy from a photon of light depends on the chromophore, its linkage to the protein, and the surrounding protein environment. To understand the molecular mechanisms by which a chromophore and protein interact to undergo a light cycle, we are studying photoactive yellow protein (PYP), a 14-kDa water-soluble photoreceptor from Ectothiorhodospira halophila with a photocycle similar to that of sensory rhodopsin. Here, we report the cloning and sequencing of the pyp gene and the chemical identification of both the chromophore and its covalent linkage to the protein. Elemental composition data from high-resolution mass spectrometry of a proteolytically derived chromopeptide, pH titrations and UV-visible spectroscopy of the protein-bound and chemically released chromophore, and fragmentation mass spectrometry of the liberated chromophore amide were combined with results from the 1.4-A-resolution protein crystal structure to identify the chromophore in PYP as a 4-hydroxycinnamyl group covalently bound to the sole cysteine residue via a thioester linkage. While 4-hydroxycinnamate is a metabolic product of the phenylpropanoid pathway and a key molecule in plant stress response, this is the first report of covalent modification of a protein by this group. In the dark (yellow) state of PYP, the protein stabilizes the chromophore as the deprotonated phenolate anion. By combining our biochemical characterization of the chromophore with other published observations, we propose a chemical basis for the photocycle: following the initial absorption of a photon, the photocycle of PYP involves protonation of the chromophore to a neutral phenol form corresponding to the observed photobleached intermediate.

Amino Acid Sequence↗
PubMed1994

[Urologic complications in sacrococcygeal agenesis].

In 11 children with partial sacrococcygeal agenesis without concurrent patent cystic myelomeningocele clinical symptoms were analyzed as well as the character of dysfunction of the bladder and therapeutic results. The cause of urinary incontinence, which was a constant symptom, was not diagnosed correctly in six children. Due to impaired innervation, mostly of the supranuclear type, the bladder dysfunction had more frequently the character of impaired evacuation (8 children) always with obstruction of the flow at the level of the external sphincter. Areflexia of the detrusor was found in three children. In this group changes of the upper urinary pathways were found in four children (three times unilateral reflux, twice dilated ureters, twice also pyelonephritis), always in conjunction with a bladder of low compliance. The impaired storage of urine found in three children was due to hyperreflexia of the bladder. After surgery (three children), conservative treatment (8 children) and their combination progression of changes of the upper urinary pathways was arrested and the degree of incontinence improved or was completed relieved during the 18-78-month follow-up of all patients. Extirpation of the associated subcutaneous lipomyelomeningocele and release of the attached spinal cord in three children aged 5, 10 and 12 years did not lead to improvement of the nervous lesion in any of the patients.

Adolescent↗
PubMed1993

Catalytic contribution of flap-substrate hydrogen bonds in "HIV-1 protease" explored by chemical synthesis.

An analogue of "HIV-1 protease" was designed in which the ability to donate important water-mediated hydrogen bonds to substrate was precisely and directly deleted. Chemical ligation of unprotected peptide segments was used to synthesize this "backbone-engineered" enzyme. The functionally relevant amide -CONH- linkage between residues Gly49-Ile50 in each flap of the enzyme was replaced by an isosteric thioester -COS- bond. The backbone-engineered enzyme had normal substrate specificity and affinity (Km). However, the catalytic activity (kcat) was reduced approximately 3000-fold compared to the native amide bond-containing enzyme. Inhibition by the reduced peptide bond substrate analogue MVT-101 was unaffected compared with native enzyme. By contrast, the normally tight-binding hydroxyethylamine inhibitor JG-365 bound to the backbone-engineered enzyme with an approximately 2500-fold reduction in affinity. The reduced catalytic activity of the -Gly49-psi(COS)-Ile50-backbone-engineered enzyme analogue provides direct experimental evidence to support the suggestion that backbone hydrogen bonds from the enzyme flaps to the substrate are important for the catalytic function of the HIV-1 protease.

Amino Acid Sequence↗
PubMed1993

Structural engineering of the HIV-1 protease molecule with a beta-turn mimic of fixed geometry.

An important goal in the de novo design of enzymes is the control of molecular geometry. To this end, an analog of the protease from human immunodeficiency virus 1 (HIV-1 protease) was prepared by total chemical synthesis, containing a constrained, nonpeptidic type II' beta-turn mimic of predetermined three-dimensional structure. The mimic beta-turn replaced residues Gly16,17 in each subunit of the homodimeric molecule. These residues constitute the central amino acids of two symmetry-related type I' beta-turns in the native, unliganded enzyme. The beta-turn mimic-containing enzyme analog was fully active, possessed the same substrate specificity as the Gly16,17-containing enzyme, and showed enhanced resistance to thermal inactivation. These results indicate that the precise geometry of the beta-turn at residues 15-18 in each subunit is not critical for activity, and that replacement of the native sequence with a rigid beta-turn mimic can lead to enhanced protein stability. Finally, the successful incorporation of a fixed element of secondary structure illustrates the potential of a "molecular kit set" approach to protein design and synthesis.

Amino Acid Sequence↗
PubMed1990

A brief contact of native whole blood with adenosine diphosphate (ADP) promotes the release of the contents of platelet alpha granules but not dense bodies and increases platelet retention to glass bead columns.

We have previously demonstrated that a brief contact of native whole blood with ADP, promotes a dose dependent release of the contents of platelet alpha granules. In the present study we have shown that in our system there is not a parallel release of the contents of platelet dense bodies as measured by the release of serotonin (5 HT). This early and partial platelet activation determines an increase in platelet retention in glass bead columns. After exactly 15 seconds of activation of native whole blood from 6 healthy volunteers with ADP, in fact, there was a significant fall in the platelet count following the flow of native whole blood across glass beads. A significant decrease (from x = 182,000 +/- 13,700 to x = 120,000 +/- 8,00/microliters p less than 0.001) was present when the blood was stimulated with 0.4 microM ADP final concentration. These results suggest that early, partial platelet activation by ADP could facilitate their possible adhesion to a suitable surface exposed along the vascular tree.

Adenosine Diphosphate↗
PubMed1989

The optimal therapeutic range for oral anticoagulant treatment as suggested by fibrinopeptide A (FpA) levels in patients with heart valve prostheses.

Fibrinopeptide A is a good marker of in vivo thrombin formation. The aim of oral anticoagulants (OA) is to lower in vivo thrombin formation. We therefore assessed FpA levels on several occasions in 38 patients receiving OA for artificial heart valve prostheses and in 20 patients receiving OA for biological heart valve prostheses. The mean FpA level, 1.82 ng ml-1 (SEM 0.14, n = 176), in patients with artificial valves was significantly higher than the mean, 1.02 ng ml-1 (SEM 0.4), obtained in 41 healthy subjects (P = 0.01). FpA mean value for biological valves was 1.41 ng ml-1 (SEM 0.14, n = 76), which was not significantly higher than controls (P = 0.08). A decrease in FpA levels, for both artificial and biological heart valve prostheses, was associated with a parallel increase in the intensity of anticoagulation. When considering FpA values obtained in the optimal therapeutic range for oral anticoagulant treatment, (International Normalized Ratio [INR] between 3 and 4.5), the mean level for artificial valves, 1.87 ng ml-1 (SEM 0.18, n = 102), was significantly higher than the mean value, 1.25 ng ml-1 (SEM 0.16, n = 55), obtained for biological valves. From a biological point of view, this indicates that artificial valves should be kept at a higher intensity of anticoagulation.

Administration, Oral↗
PubMed1986

Adenosine diphosphate (ADP)-induced alpha-granules release from platelets of native whole blood is reduced by ticlopidine but not by aspirin or dipyridamole.

A brief contact between native whole blood and ADP promotes a dose-dependent release of platelet alpha-granules without a fall in the platelet number. We assessed the "ex vivo" effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the alpha-granules release for an ADP stimulation of 0.4 (p less than 0.02), 1.2 (p less than 0.01) and 2 microM (p less than 0.01). No drug, however, completely inhibits this early stage of platelet activation. The platelet release of alpha-granules may be related to platelet shape change of the light transmission aggregometer and may be important "in vivo" by enhancing platelet adhesiveness and by liberating the platelet-derived growth factor.

Adenosine Diphosphate↗
PubMed1966

Fine structure of the human ovum in the pronuclear stage.

A penetrated ovum was recovered from the oviduct of a 33 year old surgical patient who had had sexual intercourse 26 hr before the operation. The ovum was in the pronuclear stage. The ooplasmic organelles were mainly represented by mitochondria, endoplasmic reticulum components, and Golgi elements. Small vesicles were found in the space between the two sheets of the pronuclear envelope. These vesicles appeared to be morphologically similar to the ER vesicles in the ooplasm and were considered to be involved in pronuclear development. Numerous annulate lamellae were seen in the ooplasm as well as in the pronuclei. Ooplasmic crystalloids were also observed. These were thought to represent cytoplasmic yolk. Remnants of the penetrating spermatozoon were found in close relation to one of the pronuclei. The fine structure of the first and second polar body is also described. The nuclear complement of the first polar body consisted of isolated chromosomes, whereas the second polar body contained a membrane-bounded nucleus. In consideration of the possibility that polar body fertilization may take place, these differences in nuclear organization could be of importance. Other recognizable differences between the two polar bodies were presence of dense cortical granules and microvilli in the first polar body, and absence of these structures in the second. These dissimilarities were considered to be related to the organization of the egg cytoplasm at the time of polar body separation.

Adult↗