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Biomedical subjects

M A Martin

Publications and source records attributed to M A Martin.

At least 127 records · Page 7Linked to original sources
PubMed1991

Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation.

cis-acting inhibitory region (IR) sequences were identified within the gag/pol gene of the human immunodeficiency virus type 1 (HIV-1) by using a novel feedback-stimulated, rev-independent tat reporter gene to screen HIV-1 sequences in transient expression assays. Two regions, a 1,295-nucleotide segment in the gag gene (IR-1) and a 1,932-nucleotide segment of the pol gene (IR-2), each inhibited reporter gene expression 10- to 20-fold. IR-1 and IR-2 both contained subsequences which inhibited reporter gene expression. Introduction of IR sequences into a heterologous reporter plasmid, pCMV-CAT, resulted in decreased chloramphenicol acetyltransferase expression, suggesting that the inhibitory effect was not restricted to a reporter gene under the control of the HIV-1 promoter. The presence of HIV IR sequences in cis did not alter relative levels of reporter gene RNA; however, fractionation studies revealed IR-containing RNA accumulated in the nucleus. These findings demonstrate that IR sequences within the gag/pol region affect gene expression by altering the cellular distribution of viral RNA.

Base Sequence↗
PubMed1991

Variable role of the long terminal repeat Sp1-binding sites in human immunodeficiency virus replication in T lymphocytes.

The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains three binding sites for the transcriptional factor Sp1. In order to investigate the role that the Sp1-binding sites play in regulation of HIV replication, we have introduced a deletion of all three Sp1-binding sites into the LTR of an infectious molecular clone of HIV. Viral stocks have been prepared from this mutant virus, designated dl-Sp, and these stocks have been used to study its replicative ability in human T cells. The dl-Sp virus replicated efficiently in MT4 cells and in phytohemagglutinin-stimulated human peripheral blood lymphocytes, but it replicated poorly and with delayed kinetics in A3.01 (CEM) T cells unless those cells had been treated with the cytokine tumor necrosis factor alpha. Gel retardation assays to study the levels of DNA-binding proteins present in these cells showed that NF-kappa B activity could be detected in the nuclei of MT4 cells but not in A3.01 cells unless they had been treated with tumor necrosis factor alpha. Thus, the presence of NF-kappa B activity appeared to be required for efficient replication of an HIV whose LTR Sp1-binding sites had been deleted. This suggests that NF-kappa B can functionally compensate for Sp1 in activating HIV replication. The HIV LTR is therefore similar to the promoter-enhancer units of other viruses in that it is composed of multiple functional elements that may contribute differently to viral replication depending on the levels of DNA-binding proteins present in the target cells.

Animals↗
PubMed1991

Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types.

Starting with a replication-incompetent molecular clone of human immunodeficiency virus type 1, lacking all the NF-kappa B and Sp1 binding sites present in the native long terminal repeat (LTR), proviruses containing reconstructed LTRs with individual or combinations of NF-kappa B and Sp1 elements were generated and evaluated for their capacity to produce virus progeny following transfection-cocultivation. Virus stocks obtained from these experiments exhibited a continuum of replicative capacities in different human T-cell types depending on which element(s) was present in the LTR. For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites), a hierarchy of cellular permissivity to virus replication (peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat) was observed. Of note was the associated emergence of second-site LTR revertants which involved an alteration of the TATA box. These results suggest that the human immunodeficiency virus type 1 LTR possesses functional redundancy which ensures virus replication in different T-cell types and is capable of changing depending on the particular combination of transcriptional factors present.

Base Sequence↗
PubMed1991

A comparative study of the activity of first and second generation cephalosporins and their combinations with beta-lactamase inhibitors against Bacteroides fragilis.

The sensitivity of 160 strains of Bacteroides fragilis, 74 beta-lactamase-positive and 86 negative, to two first generation and four second generation cephalosporins, alone and in combination with clavulanic acid and sulbactam, was investigated. For the susceptibility test the dilution method in agar was used. The detection of beta-lactamase production by this micro-organism was performed by means of the method using chromogenic cephalosporin of Nitrocefin. In both strains an important improvement in the activity of cephalothin, cephazolin, cefonicid and cefamandole was noted when they were combined with the two inhibitors. In combinations of cefoxitin and cefmetazole, no significant improvement was evident in the values of the parameters studied in the beta-lactamase-producing strains; and even in beta-lactamase-negative strains these values showed only a slight increase.

Bacteroides fragilis↗
PubMed1991

Epidemiology and clinical impact of gram-negative sepsis.

Gram-negative sepsis, which was uncommon in the pre-antibiotic era, has become a major problem throughout the latter half of this century, particularly among persons with severe underlying diseases. The development of antibiotics with dramatic bactericidal activity against these pathogens and advances in supportive care have improved the outlook. Nonetheless, the mortality remains high among the growing numbers of elderly patients with chronic illnesses, immunocompromised patients, patients subjected to invasive procedures, and patients in critical care units colonized with highly antibiotic-resistant flora.

Bacteremia↗
PubMed1990

Determination of extracellular/intracellular fluid ratios from magnetic resonance images: accuracy, feasibility, and implementation.

This study determines the accuracy and feasibility of using localized spin-lattice (T1) relaxation time measurements from magnetic resonance (MR) images to follow changes in extracellular/intracellular fluid ratios in defined subvolumes of living tissue. A red blood cell suspension was used as a test system and a simple two-compartment model incorporating fast exchange was found to suffice for the conversion of T1 values to volume ratios. The technique requires the addition of gadolinium-DTPA to the model system to selectively enhance relaxation in the extracellular fluid space. No detectable amount of gadolinium-DTPA was found to enter the intracellular fluid space, and all magnetization decay plots obtained from both intracellular constituents and complete RBC suspensions consisted of a single exponential. Both of these results are compatible with assumptions underlying our physical model. The NMR-determined fluid ratio values were compared to those measured via the microhematocrit technique. Partial saturation image-mode determinations are strongly correlated to microhematocrit data (R2 = 0.945) and indicate that localized cell volume changes may be followed with a sensitivity of +/- 2.2%. These values compare favorably with those produced when nonimaging inversion-recovery techniques are used to determine the MR hematocrit (R2 = 0.962, sensitivity = +/- 1.1%). This technique, with modification, should be applicable to the comparison of ratios of extracellular/intracellular fluid volumes in structurally complex tissues where small subvolumes of homogeneous cell structure could be examined.

Body Fluids↗
PubMed1990

The homeless mentally ill and community-based care: changing a mindset.

The care of persons with severe, persistent and disabling mental illness has received increasing attention during the past ten years. This focus is due, to some extent, to the increased visibility of a subset of this population, the large number of individuals with psychiatric problems who have become homeless. These men and women, who are without homes or in temporary residences, present a sophisticated array of needs and a multiplicity of problems which have rendered most communities impotent to provide appropriate and adequate rehabilitative services. To date, there is no "perfect" community-based system of care for these men and women. What exists is a hodge-podge of shelter, outreach and drop-in center services. Most of these provide little more than a bed (or a chair) to sleep on, a hot meal and refuge from inclement weather. This article discusses some of the issues and assumptions that inhibit and foster the development and provision of a comprehensive system of community-based care for persons with serious and persistent mental disorders who have become homeless. A framework, useful in reconceptualizing the clients, the services and the interaction between them is presented.

Community Mental Health Services↗
PubMed1990

Replication of HIV-1 in primary monocyte cultures.

A subpopulation of human monocytes began to express surface CD4 during its in vitro cultivation in the presence of recombinant M-CSF and became susceptible to infection with an isolate of HIV-1 [AD-87(M)], originally recovered from a seropositive individual by cocultivation with primary monocytes. Approximately 10% of the adherent cells synthesized CD4; a similar fraction was infectable with AD-87(M) and produced high levels of progeny particles. An interesting feature of the HIV-1 infection of primary monocytes was the detection of gp 160/120 inside but not on the surface of virus-producing cells. The implication of these results on HIV infection in vivo will be discussed.

Blotting, Northern↗
PubMed1990

The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release.

A deletion mutation affecting vpu was introduced into an infectious molecular clone of human immunodeficiency virus type 1, and the resultant phenotype was examined after infection of human T lymphocytes. The absence of vpu resulted in an accumulation of cell-associated viral proteins and impaired the release of progeny virions. Both electron microscopic and biochemical analyses indicated that a large proportion of the mutant particles was attached to the surface of infected cells. Significant variation in the size and shape of these progeny virions was observed. In addition, intracytoplasmic particles, some of which formed aberrant budding structures, were visualized in T cells infected with the vpu mutant. Indirect immunofluorescence analyses of cultures inoculated with wild-type virus with use of a vpu-specific antiserum demonstrated that vpu is mainly localized to a perinuclear region in the cytoplasm of virus-producing cells.

Amino Acid Sequence↗
PubMed1990

Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection.

Although many experimental treatments are being evaluated for the treatment of acquired immunodeficiency syndrome (AIDS) and symptomatic HIV infection (ARC), only zidovudine (AZT) has been shown to prolong the lives of such patients. This article reviews the authors' experience with 101 patients with AIDS (73) or ARC (28) treated with AZT at a public hospital clinic in Los Angeles County. The patients were seen at least monthly for five to 87 weeks (means = 27.6) by nurse practitioners and physicians. Initiation of AZT therapy required a CDC-defined diagnosis of AIDS or an absolute CD4 lymphocyte cell count of 200/mm3 or less. The demographic distribution of the patient population was as follows: Caucasian, 59; Hispanic, 22; and black, 20. The mean age of the population was 37.4 years, and the predominant risk factor was homosexual contact (76 percent). Forty-one patients required modification of their AZT doses secondary to anemia, neutropenia, a combination of anemia and neutropenia, or for personal reasons. Thirty-four of the 41 patients (83 percent) never returned to full dose after reductions. The majority of these patients (81 percent) had AIDS and/or CD4 lymphocyte counts less than 150/mm3. Hematologic toxicity was common; 27 percent required blood transfusions. Of the 101 patients followed from five to 87 weeks, 87 percent were surviving after a mean of 45 weeks of AZT therapy. The article underscores the effectiveness of AZT in prolonging the lives of AIDS and ARC patients.

AIDS-Related Complex↗
PubMed1990

Clinical significance of free-floating venous thrombi.

To evaluate the fate of free-floating venous thrombi, venous duplex scans of 5238 consecutive lower extremities over a 2 1/2 year period were reviewed. Acute deep venous thrombosis was found in 732 cases. Eighty-two free-floating deep venous thrombi were diagnosed in 73 of these patients. Nine of 72 patients (13%) had pulmonary emboli as diagnosed by ventilation perfusion scanning or pulmonary angiography or both. Seven of these patients (78%) had a pulmonary embolus before the initial duplex scan. Two (22%) had a pulmonary embolus after the diagnosis of free-floating thrombus. Thirty-three of 73 patients (45%) had follow-up of free-floating thrombi by duplex scanning performed in the acute period (less than 30 days): 18 (55%) showed attachment of the free-floating thrombus, three (9%) showed progression in size of the free-floating tail, and eight (24%) showed decrease in size or resolution of the free-floating thrombus. Four (12%) showed persistent thrombus without evidence of resolution, propagation, or attachment. In conclusion, free-floating venous thrombi occurred in 10% of cases of acute deep venous thrombosis. Only 13% of free-floating thrombi were associated with clinically significant pulmonary emboli, confirmed by ventilation perfusion scanning. Usually the embolus occurred before diagnosis of free-floating thrombus. Most free-floating thrombi followed noninvasively by duplex scanning do not embolize, but rather they become attached to the vein wall or resolve.

Adult↗
PubMed1989

Plasma tumor necrosis factor levels in patients with presumed sepsis. Results in those treated with antilipid A antibody vs placebo.

Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with Streptococcus pneumoniae. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with Enterobacter cloacae bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for Haemophilus influenzae (50 pg/mL) and Bacteroides fragilis (120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis.

Antibodies, Monoclonal↗
PubMed1989

Coagulase-negative staphylococcal bacteremia. Mortality and hospital stay.

OBJECTIVE: To determine the attributable mortality and the excess length of hospital stay resulting from coagulase-negative staphylococcal bacteremia. DESIGN: Matched historical cohort study. SETTING: Large university-based tertiary care center. PATIENTS: Of 171 patients with hospital-acquired coagulase-negative staphylococcal bacteremia identified by prospective surveillance of nosocomial infections from 1 July 1984 to 30 June 1987, 118 met criteria for the study and were matched to a control patient by age, sex, primary diagnoses, operative procedures, and date of admission. MEASUREMENTS AND RESULTS: Success was achieved in 621 of 650 (96%) variables used for matching. Staphylococcus epidermidis accounted for 92% of the bacteremias. Twenty cases (17%) had evidence of septic shock, and 10 had disseminated intravascular coagulation. The mortality rate in cases was 36 of 118 (30.5%) compared with 20 of 118 (16.9%) in controls. The attributable mortality was 13.6% (95% CI, 4.2 to 22.9) and the risk ratio for dying was 1.8 (95% CI, 1.2 to 2.7; P = 0.006). The median length of stay was 46 days for cases and 37.5 for controls (P = 0.0002). CONCLUSIONS: Coagulase-negative staphylococci, the leading organisms causing hospital-acquired bacteremias, are associated with mortality in excess of that due to the underlying diseases alone. Moreover, they significantly prolong the length of hospital stay. These findings show the importance of coagulase-negative staphylococcal bacteremia in hospitalized patients.

Adolescent↗