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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 271 records · Page 15Linked to original sources

A discrete cis element in the human immunodeficiency virus long terminal repeat mediates synergistic trans activation by cytomegalovirus immediate-early proteins.

The major immediate-early (IE) promoter of human cytomegalovirus directs the expression of several differentially spliced and polyadenylated mRNAs that encode isoformic proteins with apparent molecular masses of 55, 72, and 86 kDa. All of these proteins are potent transcriptional regulatory proteins. We are interested in the collateral interactions between human cytomegalovirus and human immunodeficiency virus (HIV) in the context of dual infection of a cell. The roles of the specific IE protein isoforms and their respective response elements involved in trans activation of the HIV long terminal repeat (LTR) are not known. Here we present evidence that major IE proteins IE86, IE72, and IE55 are capable of trans-activating the HIV LTR in a T-cell line, HUT-78. The IE55 isoform noncooperatively stimulates the HIV LTR in the presence of either isoform IE72 or IE86. Interactions between isoforms IE72 and IE86, however, result in strong synergistic activation of the LTR. Our results suggest that a specific 155-amino-acid protein domain that is unique for the IE86 protein participates in this synergic interaction. Point mutational analysis of the LTR identified a distinct cis-acting target site, located between nucleotide positions -174 and -163, that mediates exclusively synergistic trans activation by the IE72 and IE86 proteins. Finally, this study underscores the role of a cellular intermediate(s) for communicating the synergic interactions between two IE trans activators.

Amino Acid Sequence↗

Metabolic and functional consequences of blunted myocardial reactive hyperemia.

This study determined whether the rapidity of myocardial metabolic and contractile recovery after brief coronary occlusion depends upon the intensity of reactive hyperemia. We also tested the hypothesis that coronary flow rate modulates contractility after brief myocardial ischemia, independent of changes in phosphorus metabolites. Eight open-chest pigs were studied with phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy with 14 s time resolution. After a 29-s anterior descending coronary occlusion, peak Doppler coronary flow velocity was alternately unrestricted (normal hyperemia, 443 +/- 40% of control) or limited to 159 +/- 9% of control. During 29 s coronary occlusion, phosphocreatine-to-inorganic phosphate ratio (PCr/Pi) and systolic segment shortening in the ischemic region fell to 28 +/- 4 and 7 +/- 7% of control, respectively. With normal hyperemia, PCr/Pi and segment shortening recovered within 29 s. With blunted hyperemia, recovery of both parameters was delayed an additional 29-43 s, associated with reduced subendocardial blood flow (measured with radioactive microspheres) and persistent intracellular acidosis. However, the relationship between segment shortening and PCr/Pi was unaffected by the intensity of reactive hyperemia. Thus blunted reactive hyperemia significantly delays metabolic and contractile recovery from brief ischemia, probably via transient maldistribution of transmural perfusion. However, coronary blood flow rate does not independently modulate contractility after brief reversible ischemia.

Adenosine Triphosphate↗

Disseminated, miliarial type lymphocytoma cutis. A report of two cases.

The disseminated, miliarial type of lymphocytoma cutis (DMLC) is a clinicopathologic subtype of lymphocytoma, characterized by multiple, 1-2 mm translucent asymptomatic papules located in the exposed areas of the head and neck. DMLC represents a multifocal hyperplasia of B-lymphocytes with follicular differentiation and formation of follicular germinal centres. The evolution of the disease is characteristic, with some of the lesions resolving and other progressing to nodules or pseudolymphomas. The disease has a chronic course, with complete resolution in one to several years.

Aged↗

Attitudes of medical practitioners towards alcohol and alcohol consumption.

Doctors frequently come into contact with problems arising from alcohol abuse and such direct exposure would be expected to make them highly aware of such circumstances. A total of 224 medical practitioners (173 men and 51 women) were studied. The questionnaire contained 124 items pertaining to socioprofessional and demographic information, opinions and attitudes. In our study 5.91% of those doctors questioned did not consider alcohol a drug. When faced with an alcoholic in the family or in the home, 45.53% said they would seek medical help for the person involved, while 40.17% responded that they would prefer to go to an alcoholics' or ex-alcoholics' association. The number of years in practice was related, together with age, to variables of attitude. Older practitioners with longer practices were less knowledgeable about alcoholism and ascribed less importance to an accurate diagnosis and appropriate treatment.

Alcoholism↗

Imaging of arthropathies and disorders of connective tissue.

The evolution of diagnostic imaging has been recently characterized by a wish for a better understanding of pathogenesis of diseases and by technologic progress. Many authors published papers reexamining old myths and old concepts of osteoarthritis. Correlations between clinical data, radiologic data, and MR findings have allowed better definition of the characteristics of osteoarthritis of the knee. MR imaging is of great value in evaluating rheumatoid arthritis in the early stages and in certain locations such as the cervical spine and temporomandibular joint. New imaging techniques, especially CT and MR imaging, are also useful for accurately diagnosing Andersson lesions and cauda equina syndrome in ankylosing spondylitis as well as sacroiliac joint abnormalities in Crohn's disease.

Arthritis↗

Trans-dominant Tat mutants with alterations in the basic domain inhibit HIV-1 gene expression.

The Tat protein of the human immunodeficiency virus type 1 (HIV-1) is required for efficient viral gene expression. By means of mutational analyses, several domains of the Tat protein that are required for complete activation of HIV-1 gene expression have been defined. These include an amino-terminal activating domain, a cysteine-rich dimerization domain, and a basic domain important in the binding of Tat to the trans-activation response element (TAR) and in Tat nuclear localization. Recently, we described a mutation, known as delta tat, which resulted in a protein with a truncated basic domain. This protein had a "trans-dominant" phenotype in that it inhibited wild-type Tat activation of the HIV-1 LTR. To further characterize the requirements for generating a Tat trans-dominant phenotype, we constructed a variety of Tat proteins with truncations or substitutions in the basic domain. A number of these proteins showed a trans-dominant phenotype. These Tat mutants also inhibited activation of the HIV-1 LTR by a protein composed of Tat fused to the prokaryotic R17 (phage MS2) RNA-binding protein in which the R17 recognition element was inserted in the HIV-1 LTR in place of TAR. Thus, an intact TAR element was not required for this inhibition. We also studied the cellular localization of Tat and a trans-dominant Tat mutant by means of immunofluorescence staining with the use of antibodies reactive to different domains of the Tat protein. The results indicated that Tat becomes localized predominantly in the nucleus both in the presence and absence of the trans-dominant Tat construct, suggesting that the trans-dominant mutant does not inhibit Tat nuclear localization. These studies further define the requirements for the creation of trans-dominant Tat mutants, and suggest that the mechanism of trans-dominant Tat inhibition may be either the formation of an inactive complex between wild-type and mutant Tat or sequestration of cellular factors involved in regulating HIV-1 gene expression.

Amino Acid Sequence↗

[Imaging of infectious sacroiliitis].

About 11 cases of various infectious sacroiliitis, the authors discuss the clinical, biological and radiological findings. Acute and subacute infectious sacroiliitis can be associated with another arthritis and are often accompanied by soft tissues lesions. Radiological investigations are very useful for the diagnosis, because of the unspecific clinical and biological findings. Radiography shows advanced osteoarticular remodelling but the subtle lesions are often unapparent. Bone scintigraphy shows a focal hypercaptation but is unspecific. Tomography and CT point out the erosions. With CT, soft tissues lesions are well demonstrated and a diagnostic punction with a fine needle is easily guided. MRI can indicate a bone marrow oedema and her quality for soft tissues lesions is well known; for these reasons, it could become a technic of choice.

Adolescent↗

[Magnetic resonance imaging in fractures caused by fatigue and by insufficiency].

The only important complication of a stress fracture is the true fracture. For this reason, a diagnostic should be made as fast as possible. 30 patients with stress fractures, whose 10 with magnetic resonance imaging are presented and the different radiological technics are compared. The magnetic resonance imaging, showing the first modifications inside the medullary cavity, allows a quick diagnosis in very difficult cases, when the other technics have not given the answer.

Adolescent↗

[Imaging of seronegative spondyloarthritis].

The seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome and arthritis associated with chronic inflammatory bowel diseases) are distinguished by inflammatory lesions of the sacroiliac joints, of the spine and/or a peripheral arthritis associated with the absence of rheumatoid factors. The author describes the radiological features of this group of diseases and their differential diagnosis.

Arthritis, Psoriatic↗

TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes.

Multiple regulatory elements in the human immunodeficiency virus long terminal repeat (HIV LTR) are required for activation of HIV gene expression. Previous transfection studies of HIV LTR constructs linked to the chloramphenicol acetyltransferase gene indicated that multiple regulatory regions including the enhancer, SP1, TATA and TAR regions were important for HIV gene expression. To characterize these regulatory elements further, mutations in these regions were inserted into both the 5' and 3' HIV LTRs and infectious proviral constructs were assembled. These constructs were transfected into either HeLa cells, Jurkat cells or U937 cells in both the presence and absence of phorbol esters which have previously been demonstrated to activate HIV gene expression. Viral gene expression was assayed by the level of p24 gag protein released from cultures transfected with the proviral constructs. Results in all cell lines indicated that mutations of the SP1, TATA and the TAR loop and stem secondary structure resulted in marked decreases in gene expression while mutations of the enhancer motif or TAR primary sequence resulted in only slight decreases. However, viruses containing mutations in either the TAR loop sequences or stem secondary structure which were very defective for gene expression in untreated Jurkat cells, gave nearly wild-type levels of gene expression in phorbol ester-treated Jurkat cells but not in phorbol ester-treated HeLa or U937 cells. High level gene expression of these TAR mutant constructs in phorbol ester-treated Jurkat cells was eliminated by second site mutations in the enhancer region or by disruption of the tat gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗

Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs.

A primary site of infection by human adenoviruses is lymphoid cells. However, analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported. The adenovirus early region 3 (ES) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens, thus preventing their cell surface expression with a resultant decrease in host immunologic destruction. To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells, both DNA binding and transfection analysis with the E3 promoter in both cell types were performed. These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts. Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B. Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif (L2) had minimal effects on promoter expression in HeLa cells, but resulted in dramatic decreases in expression by lymphoid cells. In contrast, mutagenesis of proximal NF-kappa B motif (L1) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small, but reproducible, increase in gene expression in lymphoid cells when coupled to the L2 mutation. Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenovirus Early Proteins↗

Percutaneous intrathoracic aspiration biopsy.

An analysis of 617 percutaneous intrathoracic aspiration biopsies (PIAB) performed on 587 patients with pulmonary and mediastinal lesions between 1954 and 1985 are presented. The effectiveness of the procedure between 1954 and 1980 and between 1981 and 1985 with a positivity of 71.6% and 84.9%, respectively, was compared. These results are statistically significant and reflect improvement in the technique employed. A greater positivity was found where the lesion measured 2 to 3 cm in diameter. Complications for this series were 7.8%. In diffuse infiltrating lesions, the positivity is less than that obtained for the whole series, and the risk of developing a pneumothorax is greater. The false-negative cases include those in which an inadequate sample was obtained for diagnosis (13.9% of the total series) and samples containing elements of the chest wall or blood (5.2%).

Adolescent↗

Repetitive stimulation increases the activation rate of skeletal muscle Ca2+ currents.

Voltage clamp experiments were conducted in frog skeletal muscle using repetitive stimulation protocols. The activation rate of Ca2+ currents increased by prepulses to depolarizing potentials or by stimulating the fiber with a frequency of 1.7 Hz at 0 mV. The effect was observable with Ca2+ or Ba2+ ions, and was clearly voltage-dependent. Physiologically, it is relevant that such activation rate increase can take place during a train of action potentials.

Action Potentials↗

Fatal fat embolism following total condylar knee arthroplasty.

Although fatality from fat emboli syndrome following total knee arthroplasty has been reported, most cases occurred following the insertion of hinged prostheses and few are documented with detailed pathology. The authors present the case of a 75-year-old patient with long-standing rheumatoid arthritis who underwent a total condylar type total knee arthroplasty procedure using an intramedullary femoral alignment system and expired 6 hours following surgery. On autopsy he had multiple organ involvement with fat emboli. Especially with the present use of intramedullary alignment systems and the increasing numbers of one-stage bilateral total knee arthroplasty procedures the potential for this problem must be recognized so that early therapy can be instituted.

Aged↗

Serotype-specific outbreak of group B meningococcal disease in Iquique, Chile.

From 1979 to August 1987, there have been 178 cases of meningococcal disease in Iquique, Chile, a city of about 140,000. The attack rate for the last 5 years has been in excess of 20/100,000 per year, more than 20 times greater than for the country overall. The mortality rate was 6%. The disease occurred in patients with ages from 4 months to 60 years, but 89% of cases were in patients less than 21 years. The largest number of cases were in the age group 5-9 years (n = 54), but the highest incidence occurred in children less than 1 year of age (72.8/100,000 per year). The male/female ratio was 1.2. Cases occurred all year round with little seasonal variation. Of the 178 cases, 173 were biologically confirmed. Serogroup analysis of strains from 135 patients revealed A = 1, B = 124, C = 10. Forty-four group B strains from 1985-7 were serotyped: 15:P1.3 = 36, 15:NT = 4, 4:P1.3 = 2, NT:NT = 2. Ten of 11 of the outbreak strains tested were sulfadiazine-resistant. This is the first recognized outbreak caused by a Gp B:15 strain in South America. It shares many of the characteristics of outbreaks caused by closely related strains in Europe, such as a predilection for older children and adolescents, sulfadiazine-resistance, and sustained high attack rates. The Iquique strain (B:15:P1.3) belongs to the same genetic clone (ET-5 complex) as the Norway (B:15:P1.16) and the Cuban (B:4:P1.15) strains.

Adolescent↗