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Biomedical subjects

P Franco

Publications and source records attributed to P Franco.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evidence that SMS 201-995 enhances the immunosuppressive effect of FK506.

Somatostatin (SS) was originally described as a growth hormone release inhibiting factor synthesised in the hypothalamus. Recently, SS and its receptor (SSTR) have been demonstrated in lymphoid tissues and seem to play a regulatory, largely inhibitory, role in immune responses. The aim of the present study was to check the immunosuppressive effect of a SS derived peptide, the octreotide (SMS 201-995) and to verify whether this molecule acted synergistically with FK506. An immunosuppressive effect of SMS was observed on the proliferation of rat spleen cells induced in vitro, either by polyclonal mitogens such as PHA or by alloantigens. With PHA stimulation, 10(-14) M SMS significantly enhanced the immunosuppressive action of 0.00001 microg/ml FK506. The addition of SMS in MLR (10(-11)-10(-9)M) increased the antiproliferative effect of both 0.0001 microg/ml and 0.00001 microg/ml FK506. In consideration of the extremely low concentration of both drugs that was required to obtain a good immunosuppression in vitro, we verified the association of FK506 and SMS in vivo in an allogeneic skin graft model that used Lewis (Lew) rats as donors and Brown Norway (BN) rats as recipients. BN treated with 0.1 mg/kg FK506 and 0.5-10 microg/kg SMS showed a significant increase in mean skin allograft survival time when compared to either a monotherapy or control group. None of the animals died or showed signs of drug-related toxicity. In conclusion, a combined therapy of SMS and FK506, administered at lower dosages than those that are considered therapeutic, led to an effective immunosuppression without any undesirable side effects.

Animals↗
PubMed1998

The effects of RGD (Arg-Gly-Asp) peptides on glaucoma filtration surgery in rabbits.

BACKGROUND AND OBJECTIVE: Integrins are the main mediators of the interaction between fibroblasts and extracellular matrix (ECM) during scar formation. The adhesion motive RGD (Arg-Gly-Asp) is contained in the ECM and is recognized by the integrin receptor. Soluble peptides containing the RGD sequence can compete with -RGD- contained in the ECM for binding to the integrin receptor and thus prevent cell adhesion and scar formation. MATERIALS AND METHODS: The peptides RGD (p602), GRGDSP (p603), GRGDSPCA (p604), and GGRGDSPCA (p605) were used in 25 glaucoma filtering surgeries in rabbits (five eyes per peptide and five with saline). RESULTS: Postoperative subconjunctival injections of peptides were given at days 0, 4, 8, 12, and 16. Bleb size, bleb survival, and signs of toxicity were examined. The GRGDSPCA and GGRGDSPCA showed an increase in bleb formation, size, and survival with no clinical signs of toxicity compared with controls (P < .008). Histopathologic evaluation confirmed inhibitory effects in scar formation with bleb formation, and transmission electron microscopy demonstrated that there was no toxicity to the ciliary body. CONCLUSION: These peptides were effective in controlling scar formation in glaucoma filtering surgery.

Animals↗
PubMed1997

Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adherence and motility.

Serine phosphorylation of human pro-urokinase (pro-uPA) by A431 human carcinoma cells results in a catalytically active molecule with reduced sensitivity to plasminogen activator inhibitor type 1. We mapped the phosphorylated seryl residues by analyzing the in vivo phosphorylation state of engineered pro-uPA variants carrying a COOH-terminal poly-histidine tag. Stably transfected A431 cells do not incorporate radioactive phosphate into tagged pro-uPA in which the serines 138 and 303 have been replaced with glutamic residues, although endogenous nontagged pro-uPA is 32P-labeled on A and B chains. Moreover, the catalytic-independent ability of the mono- and di-substituted "phosphorylation-like" variants to bind to the GPI-anchored urokinase receptor (uPAR) and promote adherence of differentiating U937, HL-60, and THP-1 myelomonocytic cells was examined. We found that glutamic residues as well as the naturally occurring phosphoserines at positions 138 and 303 abolish proadhesive ability, although they do not interfere with receptor binding. In addition, pro-uPA carrying Glu138/303 lacks the capability to induce a chemotactic response of THP-1 cells. The exclusive presence of Glu138 reduces pro-uPA proadhesive and chemotactic ability by 70-80%, indicating that a phosphoserine residue at the same position plays a major inhibitory role of myeloid cell response to pro-urokinase. The di-substitution does not affect pro-uPA ability to interact with vitronectin or to enhance binding of urea-denatured vitronectin to uPAR. However, unlike wild-type tagged pro-uPA, the di-substituted variant does not induce receptor polarization in pre-adherent U937 cells. Taken together, the data support the possibility that pro-uPA phosphorylation on Ser138/303 can modulate uPAR transducing ability.

Amino Acid Sequence↗
PubMed1997

Development of cardiopulmonary integration and the role of arousability from sleep.

The recent literature on cardiopulmonary integration in infants is surveyed here, focusing on arousals from sleep. Recent studies reported that the ontogenicity of cardiopulmonary integration cannot be evaluated independently from that of sleep-wake cycles. The issue is of importance for researchers and clinicians evaluating cardiorespiratory characteristics in infants. It also has significant implications in the understanding of clinical conditions, such as parasomnias, obstructive sleep apneas, or some cases of sudden infant death syndrome. The propensity to arouse can be evaluated by exposing the sleeper to awakening challenges. Arousal thresholds are determined by measuring the intensity of the stimulus needed to induce arousals. However, these studies are complicated by factors such as the scoring of the arousal responses. Another difficulty lies in the choice and modality of the arousal stimulus. Noise, gases, light, and nociceptive, mechanical, chemical, or temperature stimuli have all been used to induce arousals. Confounding factors modify the sleeper's responses to a given stimulus. Prenatal drug, alcohol, or cigarette use and the infant's age or, previous sleep deprivation also modify thresholds. Other confounding factors include time of the night, sleep stages, the sleeper's body position, and sleeping conditions. Arousal can also occur spontaneously because of endogenous stimuli. The literature surveyed here also covers such unresolved issues as the clinical significance of aborted arousals, or the mechanisms responsible for the arousal reactions.

Age Factors↗
PubMed1997

Vitronectin binding to urokinase receptor in human breast cancer.

Functional assembly of the plasminogen-dependent proteolytic system on the cell surface requires multiple interactions involving urokinase (uPA), urokinase receptor (uPAR), plasminogen activator inhibitors, and other molecules that mediate cell migration and adhesion. We analyzed the in vitro interaction of uPAR-containing particulate cell fractions with the amino-terminal fragment (ATF) of human urokinase and the matrix-like form of vitronectin. Binding and cross-linking of 125I-labeled ATF to crude membrane extracts from LB6-19 mouse cells overexpressing human uPARs in the presence of 25 nM urea-denatured vitronectin led to the formation of Mr 137,000, 92, 000, and 82,000 covalent complexes. Immunoprecipitation of the preformed cross-linked 125I-labeled complexes with anti-vitronectin, anti-uPA, or anti-uPAR antibodies revealed that the Mr 82,000 and 92, 000 species do contain ATF and vitronectin and identified the Mr 137, 000 species as a ternary complex formed by ATF, uPAR, and vitronectin. A similar electrophoretic pattern was displayed by acid-pretreated membranes extracted from MCF-7 breast carcinoma or HT1080 fibrosarcoma cell lines, as well as a ductal breast carcinoma specimen; the latter exhibited complex formation at concentrations of vitronectin lower than 10 nM. Finally, uPAR-vitronectin interaction was further documented by the decreased reactivity of an anti-uPAR polyclonal antibody to acid-pretreated sections of 10 breast carcinomas that had been preincubated with vitronectin. Our findings highlight the ability of uPAR to interact simultaneously with vitronectin and uPA in breast cancer, supporting a dynamic coupling of the molecular mechanisms underlying plasminogen-dependent matrix degradation and cell adhesion.

Animals↗
PubMed1996

Bonded cellulose-derived high-performance liquid chromatography chiral stationary phases. I. Influence of the degree of fixation on selectivity.

Four mixed 10-undecenoyl-3,5-dimethylphenylaminocarbonyl derivatives of cellulose, with an increasing proportion of alkenoyl groups, were synthesized and chemically bonded on allylsilica gel. The influence of the degree of fixation of the cellulose derivative on the matrix for the four resulting chiral stationary phases on their selectivity is discussed.

Cellulose↗
PubMed1996

Bonded cellulose-derived high-performance liquid chromatography chiral stationary phases. II. Influence of the porosity of the silica gel matrix on performance.

Two cellulose derivatives bearing simultaneously 10-undecenoyl and 3,5-dimethylphenylaminocarbonyl groups in different ratios were chemically bonded on allylsilica gels of different porosity. The systematic study of the effect of the silica gel pore size on the bonding of the polysaccharide derivative and on the performance of the resulting chiral supports is presented.

Cellulose↗
PubMed1996

Anterior fontanelle pressure monitoring for the evaluation of asymptomatic infants with increased head growth rate.

We studied non-invasive intracranial pressure monitoring in 20 asymptomatic infants with increased head growth rate. Both basal anterior fontanelle pressure (AFP) traces and occurrence of pressure waves were analysed and compared with normal range values previously established. Eight recordings were classified as pathological; cerebral imaging showed subdural collections or ventricular dilatation in all cases. Five out of these eight infants further developed neurological deficits and/or increase of the ventricular size, and required neurosurgical procedures. Twelve infants had normal AFP traces; six of these had normal cerebral imaging and six showed enlargement of subarachnoid spaces with normal ventricles. All of these 12 patients normalised their head growth rate and remained asymptomatic. This observation suggests that AFP monitoring may be helpful in asymptomatic infants with increased head growth rate to identify a progressive intracranial process and the potential need for a neurosurgical procedure.

Child Development↗
PubMed1996

Monoclonal antibodies against recombinant human growth hormone as probes to study immune function.

Monoclonal antibodies were raised against human recombinant growth hormone (rhGH) and those that did not cross-react with other human recombinant proteins like prolactin (PRL), interleukin 2 (IL-2), insulin, or bovine pituitary growth hormone were selected. The selected hybridoma supernatants were studied for their ability to influence T lymphocyte proliferation when induced either by a mitogen, such as phytohemagglutinin (PHA), or by alloantigen. All supernatants inhibited proliferation. Three MAbs were then purified by several passages on antimouse IgG (or IgM)-agarose columns, and characterized. These MAbs recognized three different epitopes, as revealed by competition study, although their inhibitory effect on PHA-induced T cell proliferation was quite similar. The data demonstrate that the MAbs were not cytolytic, that they did not interfere with the PHA binding to T cell membranes, and, as revealed by FACS analysis, did not bind to the membrane. Finally, these MAbs immunoprecipitated a 44-kDa molecule from PHA-activated T cell-concentrated supernatants. These data indicate that the MAbs recognized a soluble factor that plays a central role in T cell proliferation and that is probably the immune growth hormone.

Animals↗
PubMed1996

Normal sleep architecture in infants and children.

Because the collection of normative sleep data in the pediatric age group largely depends on technical issues, this article discusses various aspects of sleep recordings in infants and children. Polygraphic monitoring of sleep and waking behavior contributes to a better description of maturational stages in children, from the prenatal period to the end of adolescence. This article reviews the general characteristics of normal children's sleep and the environmental factors that influence these maturational processes. The use of polygraphic recordings to identify neurological deficits and to predict behavioral and neurological outcome in infants and children, however, does not hold great promise. The importance of polysomnographic evaluation is admitted for some major clinical conditions, such as risks for abnormal breathing or narcoleptic attacks.

Adolescent↗
PubMed1996

Decreased cardiac responses to auditory stimulation during prone sleep.

OBJECTIVE: To evaluate the relationship between body position during sleep and the infants' cardiac responses to auditory stimulation. METHODS: Thirty healthy infants with a median age of 11 weeks were studied polygraphically for one night, while sleeping successively prone and supine, or vice versa. Their behavioral and cardiac responses were recorded during rapid eye movement (REM) sleep, both before and after exposure to 90 dB (A) of white-noise. RESULTS: Ten infants were excluded from the study, because they woke up during the challenge. For the 20 infants included in the analysis, no significant difference was seen between the prone and the supine position for total sleep time, sleep efficiency, percent of REM and nonrapid eye movement sleep, number of gross body movements, transcutaneous oxygen saturation levels, mean cardiac rate, heart rate variability, number of heart rate drops; mean respiratory rate, and number or duration of central or obstructive apneas. Auditory challenges induced significantly less overall changes in heart rate, less heart rate drops, less heart rate variability, as well as fewer and shorter central apneas in the prone than in the supine position. Autoregressive power spectral analysis of the heart rate was consistent with a possible increase in orthosympathetic tone in the prone position. CONCLUSION: Prone sleeping was associated with a decrease in cardiac responses to auditory stimulation and a possible increase in orthosympathetic activity. Prone positioning could favor a reduced reactivity to danger-signaling stimuli during REM sleep.

Acoustic Stimulation↗