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C Juarez

Publications and source records attributed to C Juarez.

At least 19 recordsLinked to original sources

Staphylococcal enterotoxin B in vivo modulates both gamma interferon receptor expression and ligand-induced activation of signal transducer and activator of transcription 1 in T cells.

Superantigens (SAg) are bacterial exotoxins that provoke extreme responses in the immune system; for example, the acute hyperactivation of SAg-reactive T cells that leads to toxic shock syndrome is followed within days by strong immunosuppression. The gamma interferon (IFN-gamma) response is deeply affected in both extremes. The implication of IFN-gamma in the pathophysiology of lethal shock induced in mice after a secondary challenge with the SAg staphylococcal enterotoxin B (SEB) prompted us to study the regulation of IFN-gamma secretion and the intracellular response. We demonstrate in this study that a rechallenge with SEB becomes lethal only when given inside a critical time window after SEB priming and is associated with an increase of IFN-gamma serum release 72 h after priming. However, at this time, a selective blockade of IFN-gamma/STAT1 signaling develops in spleen cells, correlating with a lack of expression of the IFN-gamma receptor beta subunit and STAT1 in the T-cell population. Selective blockade of the STAT1 signaling pathway--while simultaneously maintaining STAT3 signaling and expression--may be a protective mechanism that shortens IFN-gamma production during the Th1 effector response. This blockade may also have consequences on switching towards a suppressor phenotype with chronic exposure to the superantigen.

Animals↗

Implication of STAT1 and STAT3 transcription factors in the response to superantigens.

The activation of STAT1 and STAT3 in response to SEB was analyzed in spleen of Balb/c mice. The intraperitoneal injection of the superantigen SEB activated STAT1 and STAT3 in spleen. Activated STAT1 almost completely disappeared in 24 h even though activated STAT3 was present for more than 48 h after SEB injection. Cyclosporine A was able to block the initial STAT1 activation, but STAT3 activation was only partially affected. SEB also increased the mRNA levels for STAT1, STAT3 and SOCS1. When a second injection with SEB was given 72 h after the first stimulus, STAT1 activation was much lower than that observed after the first stimulation with SEB and no increase in the STAT1 mRNA level was observed. Nevertheless, after this second injection, STAT3 was again activated without any significant interference from the first stimulus and the STAT3 and SOCS1 mRNA levels again increased. These data indicate that a first stimulation with superantigen re-programs cells so that they respond to a second stimulation in a different way. Understanding the mechanisms implicated in this re-programming is basic for designing therapeutic strategies in processes such as septic shock.

Animals↗

Controlled administration of penicillin to patients with a positive history but negative skin and specific serum IgE tests.

BACKGROUND: Although subjects with a positive history of immediate allergy to penicillin and negative skin test are traditionally considered to tolerate penicillin, current evidence indicates that they may develop an immediate reaction despite negative skin and serum specific IgE tests. It is thought that these patients require additional tests to confirm the diagnosis. OBJECTIVE: To assess in a large group of patients with a history of immediate allergy to penicillins but with both skin test and CAP-FEIA-negative to classical and side chain penicillin determinants, the role of controlled administration of betalactams as a diagnostic test. METHODS: A group of 330 patients with a history of immediate allergic reactions to penicillins was studied by two evaluators from the same allergy unit using the following protocol: skin tests with major and minor determinants of benzylpenicillin (benzylpenicilloyl-poly l-lysine and minor determinant mixture), amoxicillin and ampicillin, and determination of specific IgE antibodies to penicillins, by CAP-FEIA, in serum. If both tests proved negative, a controlled administration of the drug was then carried out. RESULTS: A total of 89 (27%) patients were skin test and CAP-FEIA-negative and therefore required controlled administration of the drug. Of these, 49 developed an immediate response and were therefore considered allergic, and the remainder had good tolerance after administration of both benzylpenicillin and amoxicillin. The clinical characteristics of this group were similar to the other allergic patients who were skin test or CAP-FEIA-positive, except that they were younger (P < 0.01). Twenty-two (45%) developed a response to benzylpenicillin and 27 (55%) had a selective response to amoxicillin. Although all reactions appeared within 1 h, a positive correlation was found between the dose inducing the response and the time elapsed from drug administration, for both benzylpenicillin and amoxicillin (P < 0.001). CONCLUSION: These data indicate that an important number of subjects are not correctly identified if only skin tests and/or CAP-FEIA are used and that this is particularly relevant for side chain-specific reactions and younger subjects. This suggests that new diagnostic tests are required so as to limit the use of controlled administration.

Adolescent↗

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.

BACKGROUND: Penicillin is no longer the most commonly prescribed beta-lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used beta-lactam. METHODS: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. RESULTS: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. CONCLUSIONS: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

Amoxicillin↗

Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy.

BACKGROUND: The diagnosis of IgE-mediated immediate reactions to penicillins can be supported by in vivo or in vitro tests using classical benzylpenicillin determinants. The wide variety of beta-lactams and the description of new specificities requires a re-evaluation of the different tests available. The objective was to evaluate the diagnostic capacity of Pharmacia CAP System RAST FEIA amoxicilloyl c6 (AXO) and benzylpenicilloyl c1 (BPO) in patients with a documented IgE-mediated penicillin allergy. METHODS: We studied 129 patients in five groups. Groups 1, 2, and 3 had developed an immediate reaction after penicillin treatment. Group 1 (n=19) were skin test positive to amoxicillin (AX) and/or BPO and/or minor determinant mixture (MDM); group 2 (n=29) were skin test positive to AX but negative to BPO and MDM; and group 3 (n=26) were skin test negative to all determinants, the diagnosis being confirmed by a previous repetitive history or controlled administration. Two control groups, one with nonimmediate reactions -- group 4 (n=25) -- and one with good tolerance to penicillin -- group 5 (n=30) -- were included. All samples were analyzed in vitro for AXO and BPO, and the results compared to the in vivo diagnosis. RESULTS: AX was the drug most often involved. In group 1, 53% were in vitro positive for AXO and 68% for BPO, but 74% had at least one positive test result. In group 2, only 10% had a positive in vitro test to BPO compared to 41% to AXO. In group 3, 42% had positive BPO and/or AXO in vitro tests. In the control groups 4 and 5, the negative in vitro results for AXO were 96% and 100%, and for BPO 100% and 97%, respectively. A positive correlation between specific IgE levels and the time interval from the reaction to the evaluation was found only for group 3. CONCLUSIONS: This in vitro assay is beneficial for evaluating subjects allergic to beta-lactams. It is necessary to test for specific IgE to AXO in addition to BPO in patients with immediate allergic reactions after AX. The combination of in vivo and in vitro tests for estimating IgE antibodies to penicillins is important because of the existence of patients with a positive history but negative skin test.

Adolescent↗

Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions.

BACKGROUND: In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin-homing receptor. METHODS: We studied the expression of the CLA in peripheral blood T cells from nine subjects with exanthematous reactions induced by beta-lactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1), and captopril plus tiazide (1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics. RESULTS: The expression of circulating CLA + T cells at T1 was increased compared to healthy controls (median = 20.4 vs 9.4) (P < 0.001), and the patients also expressed increased levels of HLA-DR (median = 3.8) (P < 0.005). Comparison between T1 and T2 (median = 11.2) also showed differences in levels of CLA+ T cells (P < 0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P < 0.05) and CLA+ HLA-DR+ (P < 0.05) paralleling the symptoms. CONCLUSIONS: These data support the immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.

Adult↗

Subjects with allergic reactions to drugs show in vivo polarized patterns of cytokine expression depending on the chronology of the clinical reaction.

BACKGROUND: The mechanisms involved in adverse drug reactions with an immunologic basis (ADRIB) can be antibody dependent, mainly IgE or T cell dependent (sensitized T cells). These mechanisms are regulated by a number of cytokines, including IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha, which follow the classical T(H)1/T(H)2 immunologic paradigm. Although evidence for this has been seen in ex vivo studies, the results are heterogeneous, and few in vivo studies have been carried out in subjects with ADRIB. OBJECTIVE: We studied a group of patients who experienced either immediate reactions (n = 10) or nonimmediate reactions (n = 9) to drugs to determine the cytokine pattern profile during the acute stage of the response, as well as after recovery. METHODS: PBMCs were taken at different time intervals of 24 hours or less and 7, 15, and 30 days after the onset of the reaction, and the specific cytokine transcription and production were determined by using quantitative competitive RT-PCR and ELISA, respectively. RESULTS: There was a transient polarized pattern corresponding to a T(H)1 response with IL-2, IFN-gamma, and TNF-alpha in nonimmediate reactions and to a T(H)2 response with IL-4 in immediate reactions. CONCLUSIONS: This is the first in vivo demonstration of these T(H)1/T(H)2 patterns in subjects with ADRIB and confirms that an immunologic process is occurring related to the mechanisms involved in the pathologic manifestation. These findings are relevant to the understanding of the pathophysiologic mechanisms involved in ADRIB, suggesting that further studies in this direction are warranted.

Adult↗

Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics.

BACKGROUND: Subjects with immediate reactions to penicillins and positive skin test responses may lose sensitivity if penicillin is avoided. The longer the interval between the reaction and the skin test, the greater the likelihood of having a negative result. OBJECTIVE: We sought to study prospectively the evolution of skin test sensitivity in a group of subjects allergic to penicillin with positive skin test responses to different penicillin determinants. METHODS: Skin tests were performed with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin (AX), and ampicillin at the initial evaluation and repeated 1, 3, and 5 years later if the responses were still positive. Subjects were divided into 2 groups. Group A consisted of patients with a positive skin test response to benzylpenicilloyl or minor determinant mixture, and group B consisted of those with a selective response to amoxicillin and good tolerance to benzylpenicillin. RESULTS: In group A (n = 31) after 1 year, 25 patients continued to have positive responses and 6 began to have negative responses; after 3 years, 18 continued to have positive responses, 5 began to have negative responses, and 2 were lost to follow-up; and after 5 years, 12 continued to have positive responses, 5 began to have negative responses, and 1 was lost to follow-up. In group B (n = 24) 12 had positive responses, and 12 had negative responses after 1 year; 6 had positive responses, 5 had negative responses, and 1 was lost to follow-up after 3 years; and no patients had positive responses, 5 had negative responses, and 1 was lost to follow-up after 5 years. Survival analysis showed significant differences between groups (log-rank test = 12.8; P <. 0003). CONCLUSION: Patients with a selective response to amoxicillin tended to lose sensitivity faster than those who responded to several penicillin determinants, supporting the existence of at least 2 distinct types of IgE response in patients allergic to beta-lactam.

Adult↗

Immunologic response to different determinants of benzylpenicillin, amoxicillin, and ampicillin. Comparison between urticaria and anaphylactic shock.

BACKGROUND: Subjects with IgE-mediated allergic reactions to penicillins can develop urticaria or anaphylactic shock. Urticaria is mainly associated with positivity to the major determinant of benzylpenicillin (BPO), and anaphylactic shock with minor determinants (MDM). The presence of IgG antibodies to BPO is thought to be mainly associated with urticaria, possibly protecting from anaphylactic shock. We aimed to study the skin test response to BPO and MDM, amoxicillin (AX), and ampicillin (AMP) in a group of subjects allergic to penicillins, and to evaluate the role of specific IgG. METHODS: We studied a group of patients with immediate allergic reactions to penicillins, comparing urticaria and anaphylactic shock. Skin tests were done with BPO, MDM, AX, and AMP. Specific IgE and IgG antibodies to benzylpenicilloyl-poly-L-lysine (BPO-PLL) and amoxicilloyl-poly-L-lysine (AXO-PLL) were determined by RAST and ELISA, respectively. RESULTS: Fifty-nine patients were studied (30 with anaphylactic shock and 29 with urticaria). Skin test positivity to BPO was associated with urticaria (P<0.001), and positivity to MDM, AX, and AMP with anaphylactic shock (P=0.006, P<0.001, and P=0.002, respectively). Specific anti-BPO-PLL and AXO-PLL IgG values were higher in patients than controls (P<0.001), but no differences were observed between urticaria and anaphylactic shock. CONCLUSIONS: Positivity to minor determinants of penicillins is associated more with anaphylactic shock than urticaria, but the role of IgG antibodies in helping to prevent the development of anaphylactic shock could not be confirmed.

Adult↗

Epidemiological study of the prevalence of allergic reactions to Hymenoptera in a rural population in the Mediterranean area.

BACKGROUND: Systemic allergic reactions to Hymenoptera venom occur in a percentage that varies from 0.4 to 3.3%. Epidemiological studies indicate that from 15 to 25% of the general population can be sensitized to different Hymenoptera venom as well as the fact that the degree of exposure may be related to the prevalence found in those studies. OBJECTIVE: The objective of this study was to evaluate the prevalence of insect sting allergy and the venom sensitization in a rural population to three Hymenoptera previously found in the area: Polistes dominulus (Pd), Vespula germanica (Vg) and honey bee (Hb). METHODS: A rural community located in the south-east of Spain, close to the Mediterranean Sea, was selected since the stinging Hymenoptera having been previously identified. A random sample of 310 subjects from the village census was studied. A questionnaire and a serum sample were obtained from every patient. The evaluation was conducted by a family doctor, who focused on the reactions to Hymenoptera sting, age, sex, occupation, atopia, previous Hymenoptera sting, stinging insect, interval to last sting and average stings per year. RAST to Hymenoptera venoms were also determined. RESULTS: The prevalence of systemic reactions was 2.3% (57.6% of them had a positive RAST). Large local reactions were found in 26.4% (only 28.5% of them had a positive RAST). Asymptomatic sensitization (positive RAST) was observed in 16.4% of subjects without reaction. Only a weak correlation between subjects with less than 3 years' interval to last sting exposure and positive RAST results was noted, whether they presented with a clinical reaction or not (P < 0.05). CONCLUSIONS: The prevalence of systemic sting reactions in our rural community is higher than other general populations in the same Mediterranean area, and similar to other rural populations studied. The degree of exposure influences not only the prevalence found but also the detection of specific serum IgE.

Adolescent↗

Sex determination in plants.

Sex determination is an important developmental event in the life cycle of all sexually reproducing plants. Recent studies of sex determination in many plant species, from ferns to maize, have been fruitful in identifying the diversity of genetic and epigenetic factors that are involved in determining the sex of the flower or individual. In those species amenable to genetic analysis, significant progress has been made toward identifying mutations that affect sex expression. By studying the interactions among these genes, pictures of how sex-determining signals are perceived to activate or repress male- or female-specific genes are emerging.

DNA Methylation↗

Participation of T lymphocytes in cutaneous allergic reactions to drugs.

Immunological mechanisms implicated in drug allergic reactions are not yet well understood, but there is 'in vivo' and 'in vitro' evidence that T lymphocytes are involved in these hypersensitivity reactions. The cutaneous lymphocyte-associated antigen (CLA) is the skin homing receptor and is involved in targeting a skin-selective memory T lymphocyte to cutaneous sites of chronic inflammation. We have seen that CLA expression is increased in circulating T lymphocytes of patients who develop a drug allergic cutaneous reaction, these cells are activated and their CLA values tend to become normal in parallel with the disappearance of skin symptoms, demonstrating that CD3+ CLA+ cells are involved in the immunological mechanisms responsible for the pathogenesis of the chronic inflammation process in cutaneous drug reactions.

Antigens, Differentiation, T-Lymphocyte↗

New aspects in betalactam recognition.

The data presented in this review confirm that penicillin continues to be the most well defined model for studying drug allergy. The identification of new specificities has improved the understanding of allergy to penicillins, and different well defined subgroups now exist. The capacity of humans to respond to unique penicillin determinants has shown that although penicillin is a very small molecule it can be recognized in different ways by different IgE antibodies. These well defined models have left open the possibility that other betalactams can also induce specific reactions which implies that for diagnostic purposes, in addition to classical determinants, others are required for in vitro and/or in vivo evaluation. When the different subgroups now recognized are compared, not only are there differences in the manner of hapten recognition but also in the evolution of the natural sensitivity and in the capacity for recognizing other structures. The recognition of betalactams by T cells is also important and a number of studies have shown that subjects respond specifically to some aminopenicillins or cephalosporins with good tolerance to benzylpenicillin. The confirmation that these responses can be a T-cell-mediated reaction have been reported not only in vitro by the generation of T cell lines and T cell clones but also in vivo doing skin biopsies in subjects who have developed different types of delayed cutaneous reactions [44]. More studies are needed to determine the structure of T cell epitopes and this will help for a better understanding of both the IgE and IgG-mediated reactions.

Animals↗

Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods.

The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects. Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity. In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared. Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP). Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values. Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated. Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis. Analysis of the areas defined by the ROC curves showed statistical differences among the three methods. When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays. Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods. We conclude that for quantitating IgE antibodies by RAST to the BPO determinant, BPO-SP or BPO-PLL conjugates offer advantages in sensitivity and specificity compared with BPO-HSA. These results support and extend previous in vitro studies by our group and highlight the importance of the carrier for RAST assays.

Adult↗

Inclusion body myositis and paraproteinemia: incidence and immunopathologic correlations.

Serum from 70 patients with sporadic inclusion body myositis (IBM) was subjected to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients with monoclonal proteins, 3 without, and 2 control subjects and was purified, biotinylated, and applied to muscle biopsy sections for immunocytochemistry and to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%) patients with IBM, compared with 2% of age-matched controls, had a monoclonal gammopathy characterized as IgG lambda in 9 patients, IgG kappa in 4, IgM kappa in 2, and IgA lambda in 1. The mean age of IBM patients with gammopathy was 60.6 years (range, 35-77 years), compared with 66.1 years (range, 42-80 years) of the IBM patients without gammopathy. The IgG of the patients, more often than that of the control subjects, immunostained myonuclei and recognized various muscle proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently associated with monoclonal gammopathies, which often recognize various muscle components, especially myonuclei, suggesting disturbed immunoregulation.

Adult↗

Results of a pilot study of the time to azoospermia after vasectomy in Mexico City.

In a joint pilot study by Family Health International (FHI), AVSC International, and the Instituto Mexicano del Seguro Social (IMSS), information was gathered on the determinants of azoospermia following vasectomy on 38 healthy men who chose vasectomy for contraception. The time and number of ejaculations associated with loss of sperm motility and loss of sperm eosin vital staining were also evaluated. "Azoospermia" was defined on the basis of two consecutive azoospermic semen samples collected at least 3 days apart. The single decrement life table method was used to calculate weekly gross cumulative life table rates for the time to azoospermia, zero motility, and zero viability. The Kaplan-Meier method was used to calculate the product-limit estimates of the cumulative rates for the total number of ejaculations to azoospermia, 0% motility and 0% viability. The median time to azoospermia was 10 weeks and at the end of week 20, the life table rate (+/- standard error) was 93.0 (+/- 6.30) weeks/100 men. The median number of ejaculations to azoospermia was between 25 and 30, and the cumulative rate (+/- standard error) at 60 ejaculations reached 94.5 (+/- 5.16)/100 men.

Adult↗