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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 289 records · Page 16Linked to original sources
PubMed1990

The conditioned stimulus-unconditioned stimulus-feedback feeding sequence: reply to Ellins, von Kluge, and Cramer (1990).

Taste-potentiated noise aversions have been demonstrated in rats (Ellins, Cramer, & Whitmore, 1985; Ellins & von Kluge, 1987; Holder, Bermudez-Rattoni, & Garcia, 1988). However, these aversions are apparently less readily established than taste-potentiated odor aversions suggesting that all exteroceptive stimuli are not equally well potentiated by taste (Holder et al., 1988). Despite the claims of Ellins, von Kluge, and Cramer (1990), we replicated their findings and see no inconsistency between our findings and theirs. Both sets of results are explained by a common theory of conditioning (Garcia, 1989; Garcia & Holder, 1985).

Animals↗
PubMed1990

A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat.

Regulation of human immunodeficiency virus (HIV) gene expression is dependent on specific regulatory regions in the long terminal repeat. These regions include the enhancer, SP1, "TATA," and trans-activating (TAR) regions. In addition, viral regulatory proteins such as tat and rev are important in regulating HIV gene expression. The mechanism of tat activation remains the subject of investigation, but effects at both transcriptional and posttranscriptional levels seem likely. Previous mutagenesis of the tat protein revealed that the amino terminus, the cysteine-rich domain, and the basic domain were all required for complete tat activation. Mutants of other viral trans-acting regulatory proteins, including E1A, tax, and VM65, have been identified that were capable of antagonizing the activity of their corresponding wild-type proteins. We wished to determine whether mutants of the tat protein could be identified that exhibited a similar phenotype. One mutant (delta tat) that truncated the basic domain of tat resulted in a transdominant phenotype inhibiting tat-induced gene expression of the HIV long terminal repeat but not other viral promoters. This mutant exhibited its maximal phenotype in cotransfection experiments when present in an 8- to 30-fold molar excess over the wild-type tat gene. Trans-activation of the HIV long terminal repeat by delta tat was very defective at the DNA concentrations used in these experiments. RNase protection analysis indicated that this mutant decreased tat-induced steady-state mRNA levels of the HIV long terminal repeat. Second-site mutations of the delta tat gene in either the amino terminus or cysteine region eliminated the transdominant phenotype. In contrast to tat, which was localized predominantly to the nucleolus, delta tat was present in both the nucleus and cytoplasm, suggesting that it may inhibit tat function by preventing nucleolar localization. Transdominant mutants of tat may have a role in potentially inhibiting HIV gene expression.

Amino Acid Sequence↗
PubMed1990

Limited sequence heterogeneity among biologically distinct human immunodeficiency virus type 1 isolates from individuals involved in a clustered infectious outbreak.

Human immunodeficiency virus type 1 isolates were obtained over a 3-year period from blood, brain, and lung of three patients in a clustered infectious outbreak. This included a blood donor who was initially asymptomatic but subsequently developed AIDS-related complex and two neonatal transfusion recipients who developed AIDS. Isolates from brain and lung replicated to greater than 30-fold higher levels in primary monocyte cultures than did those from blood; no growth differences on primary lymphocytes were observed. Thirteen clones were obtained from seven isolates, and env sequences were determined. The predicted amino acid sequences among these clones differed by only 0.01% but differed by 15-27% when compared to previously sequenced isolates from other patients. The level of envelope amino acid sequence divergence noted among these isolates is considerably lower than that previously reported for other human immunodeficiency virus isolates. No differences in the envelope unique to lung or brain isolates compared to blood isolates were noted. This study provides evidence that mutations in the envelope may not be necessary for disease progression and that other portions of the viral genome may contribute to cell-specific tropism.

AIDS-Related Complex↗
PubMed1990

Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste.

A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin. Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx. We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system. Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B (p less than .001). The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001). Two (15%) patients in group B developed sepsis of pulmonary origin. None of the patients on prophylactic treatment developed this complication. Although the overall mortality was similar in both groups (group A, 30% vs. group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx.

Administration, Topical↗
PubMed1990

Allergy to penicillin with good tolerance to other penicillins; study of the incidence in subjects allergic to beta-lactams.

Two hundred and eighty-eight subjects with a history of allergy to penicillin were studied for objective proof of their allergy. On the basis of skin tests, specific IgE antibody measurements and direct challenge tests. 64 patients (22%) were shown objectively to be allergic to one or more penicillins. The following tests were carried out: skin tests to benzyl-penicilloyl poly-L-lysine (BPO-PLL), minor determinant mixture (MDM), amoxycillin (AX) and ampicillin (AMP), in-vitro IgE antibody measurement to benzyl-penicilloyl (BPO) and AX and challenge with benzylpenicillin (BP), phenoxy-methyl-penicillin (PV) and amoxycillin. Forty-four cases were found to respond to benzyl or phenoxymethyl-penicillin, however, 20 were shown to be sensitive to amoxycillin and unresponsive to tests with other penicillins. The contribution that any individual test gave for establishing the diagnosis was 21.8% for skin testing with BPO-PLL, 9.3% with MDM and 12.5% with AX. Nine point three per cent were RAST positive to BPO and 1.5% to AX; 7.8% developed a positive response after challenge to BP, 7.8% to PV and 14% to AX. In 16% of the 64 positive cases more than one test was found to be positive. The challenge tests suggested that not all the penicillin-sensitive subjects had IgE-mediated reactions implying other immunological mechanisms. These results clearly demonstrate the importance of side chain-specific diagnostic reagents and challenge tests. Thirty-one per cent of the positive group or 6.9% of the total group would have been missed in this study using benzyl or phenoxymethyl-penicillin diagnostic reagents alone.

Adolescent↗
PubMed1990

Adenovirus early region 3 promoter regulation by E1A/E1B is independent of alterations in DNA binding and gene activation of CREB/ATF and AP1.

Transcription of the adenovirus early region 3 promoter is strongly induced by the adenovirus E1A protein. Previous DNase I footprinting has indicated that four regions in this promoter serve as binding sites for HeLa nuclear proteins. These include binding sites for NF-1 (site IV), AP1 (site III), CREB/activating transcription factor (ATF) (site II), and TATA (site I). To determine the relative importance of these sites in both the in vivo and in vitro transcriptional regulation of the E3 promoter, oligonucleotide-directed mutagenesis of these sites was performed. Each of these constructs was assayed by transfection onto HeLa cells in the presence of either dl434, an E1A/E1B deletion mutant, or wild-type adenovirus. Mutations of either the ATF- or AP1-binding sites but not the TATA- and NF1-binding sites resulted in severe decreases in both basal and E1A/E1B-induced transcriptional levels. These constructs were also assayed in in vitro transcription assays with cellular extracts prepared from dl434-infected or wild-type-adenovirus-infected HeLa cells. The wild-type E3 promoter was transcribed approximately 30 times more efficiently in extracts containing the E1A/E1B proteins compared with extracts lacking these proteins. Mutations of either the TATA element, the ATF site, or the AP1-binding site decreased both basal and E1A/E1B-induced transcriptional levels. Gel retardation analysis using these extracts indicated that the binding to ATF, AP1, or NF1 oligonucleotides was not altered in the presence of the E1A/E1B proteins compared with extracts lacking these proteins. Northern (RNA) blot analysis of c-jun and CREB RNA prepared from wild-type adenovirus and dl434-infected cells indicated that the levels of these RNAs were not altered by the E1A/E1B proteins. Immunoprecipitation of AP1 and CREB from both dl434- and wild-type-adenovirus-infected cells indicated that the amounts of these proteins were not significantly altered. These results suggest that E1A/E1B-induced activation of the E3 promoter does not involve activation of transcription factor genes nor a change in the DNA binding activity of important promoter-binding components. Our results are consistent with a model in which the E1A/E1B proteins either directly or indirectly alter the interactions of factors that bind to the basal E3 promoter transcription complex, thereby inducing transcription.

Adenovirus Early Proteins↗
PubMed1990

Phorbol ester induces morphological changes and acidic fibroblast growth factor RNA expression in the RD/TE 671 cell line.

The TE 671 medulloblastoma cell line was induced by phorbol-12-myristate-13-acetate (PMA) to resemble neuronal cells by both morphological and immunohistochemical criteria. Five days following PMA treatment at a concentration of 10 ng/ml, the cells acquired long cellular processes and cell growth was markedly inhibited. Immunohistochemically, PMA-treated cells stained intensely for neuron-specific enolase and were positive for neurofilaments. Northern blot analysis revealed that PMA induced the transcript for acidic fibroblast growth factor. Our data suggest that the TE 671 cell may be useful not only in the study of acidic fibroblast growth factor regulation but also as a model for embryonic tumor cell differentiation.

Cell Differentiation↗
PubMed1990

Investigations on the presence of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase, E.C.1.1.1.34) in lenses of various animal species.

The cholesterol requirements of the lens for the formation of plasma membranes are met by self-synthesis immediately after birth, this capacity, however, decreases considerably with increasing age, so that the deficit can only be met by exogenous supply. These findings are of great importance with respect to the qualitative assessment of extra-hepatical side effects of the substance class of HMG-CoA-reductase inhibitors on possible disturbances of lens transparency. In contrast to investigations of Mosley et al. (23) with rat and rabbit lenses, we did not find any activity of the HMG-CoA-reductase in our experiments with the lens cortex of calf, bovine, Beagle dog. The disturbances in lens transparency observed in chronical toxicity tests with high doses of HMG-CoA- reductase inhibitors might rather be due to the impairment of the exogenous cholesterol supply by a considerable decrease of the normal cholesterol level in the blood. The therapeutical treatment of pathologically increased blood cholesterol levels of patients should therefore not affect the transparency of human lenses. Relevant drug-safety-clinical studies confirm this experimentally substantiated supposition.

Animals↗
PubMed1990

Multicenter evaluation of triamcinolone acetonide nasal aerosol in the treatment of adult patients with seasonal allergic rhinitis.

Triamcinolone acetonide aerosol inhalation therapy is effective for the prophylactic treatment of asthma. Recently, the delivery system for this preparation has been modified for use in allergic rhinitis. A total of 180 adult patients with symptomatic seasonal allergic rhinitis participated in this double-blind, placebo-controlled, multicenter trial. Patients received either placebo or approximately 25 mg per actuation of triamcinolone acetonide aerosol per nostril, qid, for 4 weeks. Each patient kept a daily diary rating rhinitis symptoms. Both the patient and the physician also gave global evaluations of drug efficacy. Of 168 evaluable patients, significant reductions were seen at week 1, week 2, and in the overall study evaluation of ratings for intensity (P less than .001) and duration (P less than .05) of various rhinitis symptoms such as nasal stuffiness, discharge, and sneezing in the group given triamcinolone acetonide. Superiority to placebo group was evident as early as day 1 and maintained throughout the study. Both patients and physicians rated triamcinolone acetonide as significantly more effective than placebo for the duration of the study (P less than .001). There was a marked reduction in nasal smear eosinophils in the triamcinolone acetonide group. There was no difference between groups in safety evaluations including no evidence of suppression of the adrenal axis and no evidence of fungal infection. This study demonstrates that triamcinolone acetonide in a dose of 25 micrograms per nostril, qid, is effective, well tolerated, and safe in reducing symptoms in adult patients with seasonal allergic rhinitis.

Administration, Intranasal↗