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Biomedical subjects

L Gutierrez

Publications and source records attributed to L Gutierrez.

At least 19 recordsLinked to original sources
PubMed1996

Hypertonic saline challenge in an adult epidemiological survey.

Bronchial provocation tests using pharmacological agents such as methacholine or histamine are used in epidemiological studies to identify asthma despite recognition of limitations in specificity, positive predictive value and availability of reagents. Hypertonic saline (4.5%) bronchial challenge (HSBC), although less sensitive than pharmacological challenges, is reportedly highly specific in diagnosing current asthma. Added advantages are that reagents are cheap, stable and recognized by participants. Thus, HSBC may offer benefits over pharmacological tests in epidemiological surveys. This paper reports on the second field survey using the test, a study of 99 adults from the timber industry in Western Australia. The test is described and critically appraised as a practical epidemiological tool for assessing asthma prevalence. At a cutoff point of 20% FEV, fall, HSBC was positive in 8% of subjects, appeared specific for asthma, was safe, well-accepted and easy to use in the field.

Adult↗
PubMed1994

Phase II study of deoxyspergualin in metastatic breast cancer.

We conducted a phase II trial of the novel immunomodulatory/cytotoxic agent 15-deoxyspergualin in patients with metastatic breast cancer who had failed treatment with front-line chemotherapy. Thirty-eight courses of treatment were administered to fourteen patients enrolled in this trial, 25 at a dose of 1800 mg/m2/d (dose level 0) and 13 at a dose of 2150 mg/m2/d (dose level +1) administered by continuous intravenous infusion for 5 days. Treatment was well tolerated with neuromuscular side-effects (myalgias, paresthesias) and granulocytopenia (nadir granulocyte count of 0.50-0.99 x 10(9)/l) in two and three courses, respectively, as the only grade III toxicities. The neuromuscular toxicity of deoxyspergualin is probably related to the occurrence of hypomagnesemia. No partial or complete responses were observed in this study. One patient achieved a minor response but had progressive disease 65 weeks after enrollment. The response was observed coincident with an increase in T4/T8 ratio in the peripheral blood. The median time to progression for the entire cohort was eight weeks (range, 4-65 weeks). There was no clinical evidence of immunosuppression and no decrease in total peripheral blood lymphocyte counts or helper T-cells was observed. At the doses and schedule employed in this trial, deoxyspergualin does not appear to have significant activity against metastatic breast cancer resistant to front-line chemotherapy. The correlation between hypomagnesemia and neuromuscular toxicity of deoxyspergualin is an intriguing, previously unknown observation and requires further investigation.

Adult↗
PubMed1994

Acute sideroblastic anemia in active systemic lupus erythematosus.

This work describes the development of sideroblastic anemia (SA) during the clinical activity of systemic lupus erythematosus (SLE) in two patients. The cases refer to two women with SLE who developed SA during a relapse of the illness. Both patients fulfilled at least four criteria of the American Association of Rheumatology for SLE. In one patient, the treatment with prednisone was followed by the resolution of the SLE activity and the disappearance of the SA. Several years later there was no evidence of ringed sideroblasts or malignancy in the bone marrow. In the other patient, the clinical activity of the SLE and SA developed during the beginning of a septicemic event which finally led to her death. Our clinical cases allow us to show that the transitory development of SA can occur during a period of clinical activity of SLE and that its association, although infrequent, is due to a common physiopathogenic mechanism.

Acute Disease↗
PubMed1992

Instructing facilitators to support the communication of people who use augmentative communication systems.

A single-subject multiple-baseline design, replicated across three dyads, was used to examine the efficacy of instructing facilitators (i.e, significant others) to promote communication with people who use augmentative and alternative communication (AAC) systems. Facilitators were instructed in four 1-hour sessions to decrease their conversational control and provide more opportunities for the participants using AAC systems to communicate. Following instruction, facilitators decreased their rates of turn-taking and initiations and increased the proportion of turns that were responsive. Participants using AAC systems increased the frequency of their initiations. Following intervention, turn-taking and initiation patterns in the dyads were more reciprocal. Generalization occurred to the natural environment. Results suggest that facilitator instruction is an effective and efficient means of promoting greater participation in daily interactions by people who use AAC systems.

Adolescent↗
PubMed1991

Characterization of an acyltransferase acting on p21N-ras protein in a cell-free system.

We have identified a protein-acyltransferase activity in membranes from mouse fibroblasts which transfers palmitate from palmitoyl-CoA to p21N-ras. Specificity of acylation has been confirmed by linkage analysis using hydroxylamine and by peptide mapping of in vivo and in vitro acylated p21N-ras. The acylation was temperature- and time-dependent, and prevented by prior boiling of membranes, consistent with an enzymatic process. The activity was detected in membranes, but not cytosol, and co-fractionated on Percoll gradients with Golgi markers. Cytosolic p21N-ras from mouse fibroblasts, which is C-terminally modified at its CAAX sequence, was a better substrate for the enzyme that recombinant bacterially expressed, unmodified p21N-ras. The activity could be solubilised in non-ionic detergents, making it amenable to purification.

Acylation↗
PubMed1991

Spatial ability in classic dancers and their perceptual style.

The relation between spatial ability (body orientation and body awareness) and field dependence/independence was assessed by measuring performance on the Embedded Figures Test and WISC or WAIS Block Design at four different training levels in classical ballet, beginners to advanced, and a control group with no training in ballet, gymnastics, or sports (n = 70). No significant correlation was found between perceptual style or Block Design performance and body orientation or body awareness at any of the four levels of training. No significant differences were observed between the advanced group and the control group. Training in a particular type of spatial skill such as orientation within surrounding space was not related to the skill required to manipulate an abstractly represented space.

Adolescent↗
PubMed1991

Clinical assessment of gestational age: a comparison of two methods.

The ratio of fundal height (FH) to maternal abdominal length (MAL) was defined as percentage of maternal abdominal length (PMAL) and compared to FH alone in 100 consecutive uncomplicated pregnancies from the 18th week of gestation to delivery at term. Reference graphs for fetal growth evaluation were developed using these two clinical methods. The predictive value of each technique was assessed by comparing gestational age estimates in 29 additional patients at various gestational ages. The correlation coefficient between the known gestational ages and estimates by the PMAL method was .86, and between known gestational ages and estimates by the FH method, .94. Twenty more patients were evaluated by three obstetricians in a double-blind fashion to determine gestational ages by each technique. The average deviation from the real gestational age varied from 2.07 to 3.14 weeks using the FH method, and from 2.82 to 3.97 weeks using the PMAL graph. It was concluded that FH measurement correlates better with gestational age than its ratio to the MAL.

Abdomen↗
PubMed1990

Chronic naltrexone infusion: effects on innervation of rat neurointermediate lobe.

The rat pituitary neurointermediate lobe contains nerve fibers which are sensitive to the neurotoxic effects of 6-hydroxydopamine and to acute injections of the opiate antagonist, naltrexone. In the present study, naltrexone hydrochloride was administered to adult male Sprague-Dawley rats in a chronic infusion over a period of one week, using Alza osmotic pumps to determine whether a low (10(-5)M) dose could, over a longer period, also induce toxic effects on pituitary innervation. Electron microscopy of pituitary intermediate lobe fibers revealed swollen neurovesicles and membranous structures in nerve terminals, and significantly fewer normal-appearing nerve terminals, after drug infusion. Light microscopic immunostaining of paraffin sections of pituitary glands illustrated some diminution of serotonin (5-HT)-immunofluorescence in the intermediate lobe after naltrexone treatment. Immunostaining of sections from the same animals for tyrosine hydroxylase (TH) revealed intensified fiber staining in the intermediate lobe, with some regions of terminals having a swollen appearance. High pressure liquid chromatographic-electrochemical detection (HPLC-EC) analysis of neurotransmitters in selected brain areas and pituitary indicated a significant increase in norepinephrine levels in the hypothalamus. The observations suggest that intermediate lobe innervation is sensitive to low, continuously infused doses of naltrexone, which acts as a neurotoxin to produce degenerative changes in nerve terminals. The changes appear to be reflected in alterations in staining patterns of neurotransmitters, and may also affect transmitter uptake in damaged terminals.

Animals↗
PubMed1990

trans-Dominant suppressor mutations of the H-ras oncogene.

Site-directed mutagenesis of the conserved sequence motifs of p21 generated a group of mutant p21s defective in GTP binding. Some of these mutants were highly transforming, whereas others were transformation defective. Among the latter group, we found two mutants, derived from the v-H-ras oncogene by substituting the asparagine-116 with tyrosine and isoleucine, that exhibited a trans-dominant activity of suppressing the transformed phenotype of NIH3T3 cells induced by a long terminal repeat-linked c-H-ras and a wild-type v-H-ras. They caused reduction of the colony-forming efficiency in soft agar (78% in c-ras-transformed cells; 55% in v-ras cells) and morphological reversion of ras transformants. Subclones of revertants expressed a great excess of mutant p21 relative to the c-ras p21 present in these cells. These mutants were not lethal to NIH3T3 cells. Apparently, defective proteins encoded by suppressor mutants sequestered vital targets for ras function. Suppressor mutants also induced morphological reversion of NIH3T3 cells transformed by src, fes/flp, sis, and fms oncogenes, suggesting that these oncogenes function upstream to ras in the signaling pathways. Cells transformed by mos and a chemical carcinogen were unaffected.

Animals↗
PubMed1989

Post-translational processing of p21ras is two-step and involves carboxyl-methylation and carboxy-terminal proteolysis.

We have studied the post-translational processing of p21ras proteins. The primary translation product pro-p21 is cytosolic and is rapidly converted to a cytosolic form (c-p21) of higher mobility on SDS-PAGE. c-p21 is converted in turn to the membrane-bound mature palmitoylated form (m-p21) of slightly higher mobility. These processing steps are accompanied by increases in isoelectric point and in hydrophobicity as judged by Triton X-114 partitioning. Although the increases in electrophoretic mobility and hydrophobicity precede acylation we show that mutation of Cys186, which has been shown to block acylation, also abolishes the pro-p21 to c-p21 conversion. Thus the Cys186 residue is involved in the processing steps prior to acylation. We have identified two processing events which contribute to the pro-p21 conversion. Site-directed mutagenesis to insert tryptophan, which is not present in the wild type, followed by metabolic labelling with [3H]tryptophan has allowed us to map a proteolytic processing event which removes the three C-terminal residues. In addition, both the c-p21 and m-p21 forms are carboxyl-methylated. Approximately one methyl group is incorporated per molecule of p21 at steady state, which can partially account for the increase in isoelectric point. Unlike palmitate, methyl group turnover is not observed.

Amino Acid Sequence↗
PubMed1989

Targeting of oncoproteins to membranes by fatty acylation.

Post-translational modification of proteins with hydrophobic lipid-derived substituents is increasingly becoming recognized as a major route for targeting proteins to membranes. Glycosylphosphatidylinositol (GPI) anchors are found at the C terminus of a wide range of cell surface proteins, and may endow the cell with the ability to release them in a controlled fashion via specific phospholipases. We have concentrated on the direct attachment (acylation) of long-chain fatty acids (myristate, C14:0 and palmitate, C16:0) to proteins associated with the cytoplasmic face of cellular membranes. Two such proteins, the products of the src and ras oncogenes, require acylation respectively with myristate and palmitate for their membrane association and biological activity, including transformation. N-terminal myristoylation of p60src seems to be a cotranslational stable modification. However, our recent results show that post-translational modification of p21ras is a complex cascade of events involving proteolysis, methylation and thioesterification of palmitate. This last acylation event is dynamic in vivo and may regulate ras function. Enzymological studies of these modification events are in progress. A better understanding of acylation may provide targets for future pharmacological intervention.

Acylation↗
PubMed1988

Co-localization of tyrosine hydroxylase (TH)- and serotonin (5-HT)-immunoreactive innervation in the rat pituitary gland.

Adult male Sprague-Dawley rats were examined for possible co-localization of tyrosine hydroxylase (TH) and serotonin (5-HT) within innervation of the pituitary neurointermediate lobe. Use of sheep antiserum to TH and a secondary antibody coupled to fluorescein isothiocyanate (FITC), followed by rabbit anti-5-HT, then rhodamine-coupled second antibody, produced co-existent staining in some, but not all fibers of both the neural and intermediate lobes, using paraffin embedded tissues. Application of a combination of the two primary antibodies followed by sequential application of secondary antibody also resulted in co-localized antigens in selected fibers. Multiple 'classic' neurotransmitters within the same nerve terminals may modulate selected areas of endocrine tissue to control hormone release.

Animals↗
PubMed1988

Acute infusion of chemotactic or enkephalin-analog peptides into rat cerebral ventricles: scanning and transmission electron microscopy of leukocyte immigration in vivo.

Acute infusions of the formylated chemotactic peptide formyl-methionyl-leucyl-phenylalanine-lysine (FMLPL) or enkephalin analogue (Sandoz peptide) were made to the lateral cerebral ventricle of adult male rats to examine potential cellular responses within the central nervous system (CNS). Ependymal regions lining the third ventricle atop the hypothalamus were examined using scanning and transmission electron microscopy. The formylated peptide induced a significant, primarily neutrophilic cellular response in animals sacrificed 1 h after infusion. Cells were observed within and external to neuropil blood capillaries, suggestive of emigration from vasculature in response to the peptide. In contrast, the enkephalin analogue did not induce any leukocyte cellular response within the same time frame. Earlier studies have shown a monocyte/macrophage response in the same setting to the opioid peptides beta-endorphin, and to a lesser extent, methionine enkephalin. The present findings suggest that a formylated peptide is a potent stimulus for neutrophil migration within a CNS site, while opioid peptides may be variable with respect to effectiveness on cells of the immune system within the CNS, depending upon chemical configuration.

Animals↗
PubMed1987

Dynamic fatty acylation of p21N-ras.

To study the acylation of p21N-ras with palmitic acid we have used cells which express the human N-ras gene to high levels under control of the steroid-inducible MMTV--LTR promoter. Addition of [3H]palmitate to these cells resulted in detectable incorporation of label into p21N-ras within 5 min, which continued linearly for 30-60 min. Inhibition of protein synthesis for up to 24 h before addition of [3H]palmitate had no effect on acylation of p21N-ras, suggesting that this can occur as a late post-translational event. Acylated p21N-ras with a high SDS--PAGE mobility is found only in the membrane fraction, whereas approximately 50% of the [35S]methionine-labelled p21N-ras is cytoplasmic and has a lower mobility. Conversion of the acylated high mobility form to a deacylated form of slightly lower mobility can be achieved with neutral hydroxylamine, which is known to cleave thioesters. This treatment also results in partial removal of p21N-ras from the membranes. A remarkably high rate of turnover of the palmitate moiety can be demonstrated by pulse--chase studies (t1/2 approximately 20 min in serum-containing medium) which cannot be attributed to protein degradation. The data suggest an active acylation--deacylation cycle for p21N-ras, which may be involved in its proposed function as a signal transducing protein.

Acylation↗
PubMed1987

Association of sinus histiocytosis with massive lymphadenopathy and idiopathic hypereosinophilic syndrome.

A patient was evaluated because of edema, pruritus and generalized painless lymphadenopathy. Laboratory tests showed marked eosinophilia without known etiology. CT scan of abdomen revealed multiple lymph nodes in retroperitoneal area. Lymph node biopsy was reported as sinus histiocytosis, bone marrow biopsy showed hypercellularity with marked infiltration of normal eosinophils. During his admission he developed Coombs positive hemolytic anaemia. Once he was stable, a laparotomy was performed and the patient died two days later because of septic shock. Autopsy revealed sinus histiocytosis with massive lymphadenopathy (SHML) with extranodal involvement of duodenum, spleen and prostate; septic liver and spleen, pyelonephritis, marked infiltration of eosinophils in lymph nodes, spleen, liver duodenum and lungs. To the best of our knowledge, this is the first case report of the association of SHML and Idiopathic Hypereosinophilic Syndrome (HES).

Autopsy↗
PubMed1985

Evaluation of BW942C, a novel antidiarrheal agent, against enterotoxins of Escherichia coli and Vibrio cholerae.

BW942C, an enkephalin-like pentapeptide with anti-diarrheal activity, was tested against crude toxins of Escherichia coli and Vibrio cholerae in the Y-1 adrenal cell assay, rabbit ileal loop assay, and suckling mouse assay. The effects of BW942C on in vitro ion transport were measured in rabbit ileum mounted in Ussing chambers. In vitro, BW942C decreased basal short-circuit current (2.26 and 3.15 mueq cm-2 h-1 in experimental samples and controls, respectively; n = 7, P less than 0.05) and increased basal net Cl absorption (1.59 and 0.50 mueq cm-2 h-1 in experimental samples and controls, respectively; P less than 0.025). Net Na absorption was also increased, but not significantly. BW942C did not block the secretory response to a maximal dose of purified heat-stable toxin. BW942C directly enhanced intestinal fluid absorption. In the Y-1 adrenal cell assay, 5 mg of BW942C per ml inhibited the cytopathic effect caused by cholera toxin or heat-labile enterotoxin of E. coli. In the rabbit ileal loop assay, E. coli heat-stable toxin, E. coli heat-labile enterotoxin, and cholera toxin were inhibited 35 to 70% by administration of BW942C. With the suckling mouse model, the fluid accumulation caused by E. coli heat-stable toxin was ablated by prior treatment with BW942C. The drug is currently being evaluated in patients with acute secretory diarrhea to determine its effect on clinical symptoms.

Animals↗