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Biomedical subjects

M A Martin

Publications and source records attributed to M A Martin.

At least 145 records · Page 8Linked to original sources
PubMed1989

Infiltrating lobular carcinoma of the breast treated with segmental and modified radical mastectomy.

Conservative treatment of infiltrating lobular carcinoma (ILC) has previously been examined only in terms of general breast carcinoma studies. However, this lesion has been shown to differ from the more common infiltrating ductal carcinoma (IDC) in estrogen receptor (ER) status, metastatic patterns, and bilaterality. Therefore, it is necessary for the physician to consider these distinctions when planning both pre- and post-operative treatment. To determine the effectiveness of both segmental and modified radical mastectomies, the medical records of 26 patients with ILC were reviewed, and follow-up information was obtained. In addition to surgical treatment, hormonal manipulation and/or radiotherapy were used when appropriate. We found the results of a conservative approach in the treatment of this disease to be comparable to the more radical procedures with respect to overall survival and disease-free intervals. The single factor that most affected a patient's prognosis was involvement of the axillary nodes.

Adult↗
PubMed1989

Use of cellular hydrophobicity, slime production, and species identification markers for the clinical significance of coagulase-negative staphylococcal isolates.

Determining the clinical relevance of coagulase-negative staphylococci isolated from cultures of clinical specimens remains a common dilemma. One hundred eighteen strains of coagulase-negative staphylococci isolated from patients with and without indwelling foreign bodies were characterized with regard to cell-surface hydrophobicity, slime production, and species to determine the predictive value of these phenotypic markers in distinguishing clinically significant from insignificant isolates. The single test with the highest positive predictive value was hydrophobicity (79%). Hydrophobicity and speciation had the greatest combined predictive value of any two tests (89%), and this increased to only 90% when determination of slime production was added. These tests provide additional clinical information when coagulase-negative staphylococci are isolated in culture.

Bacterial Adhesion↗
PubMed1989

The human immunodeficiency virus long terminal repeat is preferentially expressed in Langerhans cells in transgenic mice.

Four lines of transgenic mice containing the HIV LTR linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT) were constructed. In each line, a characteristic tissue pattern of CAT expression was observed with detectable levels present in the eye, heart, spleen, thymus, and tail. Low levels of CAT were present in circulating lymphocytes, but CAT activity in these cells could be augmented following treatment with the mitogen phytohemagglutinin (PHA). Likewise, CAT expression was present at only low levels in circulating monocytes, but higher levels of CAT were observed in macrophages grown in the presence of various cytokines (CSF-1, GM-CSF, IL-1 alpha, IL-4, and IL-2). Furthermore, Langerhans cells recovered from skin showed higher levels of CAT activity than those observed in other cells of monocyte-macrophage lineage. These results indicate that LTR-CAT expression in cells of monocyte-macrophage lineage may increase in proportion to the degree of differentiation of these cells. These animals may be useful in the study of cell-specific determinants of LTR-directed gene activity and may serve to identify exogenous cofactors that promote the progression of HIV-related disease in vivo.

Animals↗
PubMed1989

In-vitro susceptibility of nosocomial gram-negative bloodstream pathogens to quinolones and other antibiotics--a statistical approach.

We examined the in-vitro activity of 12 antibiotics against Gram-negative bacillary isolates from 141 distinct episodes of nosocomial bloodstream infection occurring from July 1984 through November 1986. At least ten strains of each of the seven most frequently encountered species were tested. Relative potency was carefully assessed by extending the concentrations from 0.004 to 64 mg/l in microdilution tests performed in duplicate. We estimated MIC50 and MIC90 and, importantly, calculated 95% confidence intervals (CI95) for MIC90. Against all isolates, ciprofloxacin, the most potent antibiotic, had an MIC50 of 0.03 and an MIC90 of 0.13 (CI95 0.11 to 0.16 mg/l). Norfloxacin and enoxacin had MIC90 of 0.50 and 0.71 mg/l, respectively. Imipenem, ceftazidime, aztreonam, and cefoperazone had MIC90 of 1.0, 2.0, 5.3, and 5.7 mg/l, respectively. Both cefotaxime and ceftriaxone had MIC90 of 16 mg/l (CI95 13-19.7 mg/l). For tobramycin, gentamicin and amikacin, the MIC90 values were 1.4, 5.7, and 8 mg/l, respectively. Against Pseudomonas aeruginosa (n = 26), Serratia marcescens (n = 19), and Klebsiella pneumoniae (n = 26), the CI95s about the MIC90 for ciprofloxacin were 0.31-0.81, 0.07-0.23, and 0.04-0.10 mg/l, respectively. For optimal comparison of antibiotics used to treat hospital-acquired bacteraemias, only clinically significant nosocomial bloodstream isolates should be studied with regard to their antibiotic susceptibilities; the isolates should be unique (only one isolate per episode of bacteraemia occurring over a defined period of time); an adequate number of isolates of a particular species should be studied; MICs should be determined over a wide range of concentrations; and both the MIC90 and the CI95 should be reported.

4-Quinolones↗
PubMed1989

The NF-kappa B binding sites in the human immunodeficiency virus type 1 long terminal repeat are not required for virus infectivity.

Mutations were introduced into the regulatory sequences in the long terminal repeat of an infectious molecular clone of the human immunodeficiency virus. Viruses in which the NF-kappa B binding sites were deleted or ones in which one or two Sp1 binding sites were mutated still replicated efficiently in human T lymphocytes. A deletion of the two NF-kappa B sites plus the three Sp1 sites or a mutation of the tat-responsive region rendered the virus replication incompetent. Thus, the NF-kappa B sequences are not required for human immunodeficiency virus infectivity; however, a tat-responsive region is essential.

Base Sequence↗
PubMed1989

Genetic recombination of human immunodeficiency virus.

We investigated genetic recombination of the human immunodeficiency virus (HIV) in a tissue culture system. A clonal cell line expressing a single integrated HIV provirus with a termination codon affecting pol gene expression was transfected with different defective mutants derived from an infectious molecular clone of HIV. Replication-competent viral particles were recovered, passaged, and plaque purified. Restriction analyses of the proviral DNA corresponding to several of these viruses indicated that their emergence was the result of genetic recombination.

Cells, Cultured↗
PubMed1989

Functional interaction of constant and variable domains of human immunodeficiency virus type 1 gp120.

A previously reported amino acid substitution within the second conserved domain of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope results in the production of noninfectious particles. Molecular characterization of spontaneous revertant viruses, which arose during long-term cocultures of this env mutant, revealed that an amino acid change within another region of gp120 could functionally compensate for the mutation and restore infectivity. In the current study, we have introduced a conservative amino acid substitution at this second-site revertant codon and observed a marked reduction in HIV-1 infectivity. During the passage of this defective virus in cocultures, yet another revertant appeared which contained an amino acid change within a variable region of gp120 which restored infectivity to near wild-type levels. These results, in combination with other point mutations that have been introduced into the HIV-1 envelope, suggest that at least three discrete regions of gp120 may interact during the establishment of a productive viral infection. This critical step occurs subsequent to the adsorption of virions to the cell surface and either prior to or concomitant with the fusion of viral and cellular membranes.

Codon↗
PubMed1989

Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein.

We have performed a detailed analysis of the biochemical properties of the human immunodeficiency virus (HIV) type 1 vpu gene product to elucidate its function during virus replication. Our data suggest that vpu is posttranslationally modified by phosphorylation, since a 16-kilodalton phosphoprotein can be specifically immunoprecipitated with both a serum from an HIV-positive individual (HIV-positive serum) and a vpu-specific antiserum. In contrast, our results suggest that vpu is not glycosylated, even though the protein contains a potential glycosylation site. In vitro translation studies demonstrated that vpu is cotranslationally integrated into microsomal membranes, suggesting that vpu is an integral membrane protein. While vpu was found in significant quantities in virus-producing cells, the protein could not be detected in cell-free culture fluids and is therefore most likely not viron associated. Processing of viral precursor proteins was unaffected by the absence of vpu, and no differences were detected in the protein compositions of wild-type and mutant virions. However, virus release from cultures producing vpu-defective virus was found to be delayed, resulting in the intracellular accumulation of viral proteins. Our data suggest that vpu has a function in the release of virus particles from infected cells.

Base Sequence↗
PubMed1989

Transcutaneous electrical nerve stimulation and spinal cord stimulation for pain relief in reflex sympathetic dystrophy.

35 patients with the diagnosis of reflex sympathetic dystrophy in a late stage have been treated with transcutaneous electrical nerve stimulation (TENS). 6 out of the 35 were also submitted to spinal cord stimulation (SCS). The follow-up was from 10 to 36 months. The results obtained were TENS group: 25% excellent, 45% good, 10% fair, 20% poor; in the SCS group: 16.6% excellent; 66.6% good and 16.6% fair. In the long run these results are better than those obtained with sympathetic blocks and sympathectomy. TENS and SCS have no effect on osteoporosis or ankylosis.

Adult↗
PubMed1989

Serum and tissue trace metal levels in lung cancer.

Copper, zinc, magnesium, calcium and iron were measured in serum and lung tissue - tumor mass and histologically nonneoplastic tissue - from lung cancer patients and compared with serum concentrations in healthy subjects and control lung tissue obtained from patients with nonmalignant lung disease. Lung cancer patients showed a significant increase in serum Cu and Cu/Zn ratio levels and decrease in serum Zn and Fe concentrations. These findings were correlated with TNM stage of the disease, but not with histologic type of tumor. Malignant lung tissue showed a higher level of Cu, Ca, Mg, and Cu/Zn ratio and lower Zn level than that found in control samples, as well as an increase in Cu, Mg and Cu/Zn ratio concentrations with regard to histologically nonneoplastic tissue samples from the same patient. Tissue concentration of trace metals was not significantly influenced either by histologic type of tumor or clinical TNM stage. Significant correlation coefficients between serum and tissue trace metal levels were not found.

Adenocarcinoma↗
PubMed1988

A novel gene of HIV-1, vpu, and its 16-kilodalton product.

A 16-kilodalton protein expressed in cells producing the human immunodeficiency virus (HIV-1) was identified as the gene product of the vpu open reading frame. When expressed in vitro, the 81-amino acid vpu protein reacted with about one-third of the serum samples from AIDS patients that were tested, indicating that the vpu open reading frame is expressed in vivo as well. Introduction of a frame-shift mutation into the vpu open reading frame did not significantly interfere with expression of the major viral proteins in a transient expression system. However, a five- to tenfold reduction in progeny virions was observed after the infection of T lymphocytes with the mutant virus. These data suggest that the vpu gene product is required for efficient virus replication and may have a role in assembly or maturation of progeny virions.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Depolarization blunts the oxidative burst of human neutrophils. Parallel effects of monoclonal antibodies, depolarizing buffers, and glycolytic inhibitors.

The anti-neutrophil mAb PMN 7C3 and IIC4 inhibited the respiratory burst of neutrophils as measured by the generation of superoxide anion or hydrogen peroxide in response to PMA, serum-treated zymosan, and FMLP. To examine the effect of these mAb on neutrophil transmembrane potential, a fluorescent probe was used in a continuous assay. Compared with control cells, antibody-treated neutrophils were partially depolarized at rest and had a blunted response when stimulated. The F(ab)2 fragment of PMN 7C3 had similar effects on both the respiratory burst and transmembrane potential, whereas the Fab fragment did not. The unrelated antineutrophil mAb 31D8 had no effect on either the respiratory burst or on transmembrane potential. Neutrophils suspended in high potassium buffers also exhibited partial depolarization of the resting cell membrane and a blunted depolarization response to stimuli and produced less superoxide anion and hydrogen peroxide in response to stimuli than did control cells in physiologic buffer. Exposure of neutrophils to 2-deoxy-D-glucose resulted in dose- and time-dependent depression of the respiratory burst. 2-Deoxy-D-glucose also caused depolarization of the resting membrane and impaired subsequent stimulus-induced depolarization. Similar effects were seen with addition of iodoacetamide or depletion of glucose. The parallel effects of anti-neutrophil mAb, depolarizing buffers, and glycolytic inhibitors on both neutrophil membrane depolarization and activation of the respiratory burst indicate a close association between these two events. The evidence suggests that the inhibitory effects of these antibodies are mediated through partial membrane depolarization which interferes with signal transduction on subsequent stimulation of the cells. The impairment in oxidative responses to phorbol esters as well as to receptor-dependent activating agents points to interruption at a distal step, e.g., subsequent to Ca2+ mobilization.

Antibodies, Monoclonal↗
PubMed1988

Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes.

Monocytes were maintained in tissue culture for greater than 3 mo in media supplemented with rCSF-1. These cultures provided susceptible target cells for isolation and propagation of virus from PBMC of HIV-infected patients. HIV isolated into monocytes readily infected other rCSF-1-treated monocytes but only inefficiently infected PHA-stimulated lymphoblasts. Similarly, laboratory HIV strains passaged in T cell lines or virus isolated from patients' leukocytes into PHA-stimulated lymphoblasts inefficiently infected rCSF-1-treated monocytes. Persistent, low-level virion production was detected in macrophage culture fluids by reverse transcriptase activity or HIV antigen capture through 6-7 wk. Marked changes in cell morphology with cell death, syncytia, and giant cell formation were observed in monocyte cultures 2 wk after infection, but at 4-6 wk, all cells appeared morphologically normal. However, the frequency of infected cells in these cultures at 6 wk was 60-90% as quantified by in situ hybridization with HIV RNA probes or by immunofluorescence with AIDS patients' sera. Ultrastructural analysis by EM also showed a high frequency of infected cells; virtually all HIV budded into and accumulated within cytoplasmic vacuoles and virus particles were only infrequently associated with the plasma membrane. Retention of virus within macrophages and the macrophage tropism of HIV variants may explain mechanisms of both virus persistence and dissemination during disease.

Cells, Cultured↗
PubMed1988

Nosocomial aseptic meningitis associated with administration of OKT3.

An outbreak of nosocomial aseptic meningitis involving four renal allograft recipients on the transplant service occurred in July 1986, shortly after the release of the murine monoclonal antibody OKT3 for therapy for acute allograft rejection. No bacteria, fungi, or viruses were isolated from cultures of the cerebrospinal fluid of the four patients. All four had acute allograft rejection treated with OKT3 and developed signs and/or symptoms of meningitis within 72 hours of receiving the drug. To identify potential risk factors, the four patients with aseptic meningitis were compared with 12 patients on the renal transplant service in July 1986 who did not have signs or symptoms of meningitis. The development of aseptic meningitis was strongly associated with administration of OKT3. Because of this association, prospective surveillance of meningitis in patients receiving OKT3 was instituted. From November 1986 to May 1987, three (14%) of 21 patients treated with OKT3 developed aseptic meningitis. The clinical course of aseptic meningitis associated with OKT3 appears to be benign and self-limited. Nonetheless, this observation warrants continued surveillance of OKT3 therapy.

Antibodies, Monoclonal↗
PubMed1988

The use of fluorescent probes in pharmaceutical analysis.

Even though many pharmaceuticals show native fluorescence, there is also an important group of compounds which is not fluorescent. A main object of studies is to make them fluorescent, principally by using fluorescent probes through derivatisation reactions. An account of the fluorescent probes more widely used for the determination of drugs and related compounds is presented in this review paper. A wide variety of fluorescent probes is described on the basis of their ability to react specifically with various functional groups. Attention is focused on derivatisation reactions used in spectrofluorimetry and chromatographic techniques (HPLC, TLC) with fluorimetric detection. The review covers only those fluorescent probes whose use involves a chemical reaction with the analyte, and not those methods that involve physico-chemical interactions such as sensitised or charge transfer processes. Many of these derivatisation reactions have been widely used in the detection of primary and secondary amines. Reagents such as dansyl chloride, fluorescamine, o-phtalaldehyde are very well known. Other reagents have also been developed for other functional groups, for example dansyl hydrazine for compounds with a carbonyl function or 4-bromomethyl-7-methoxy-coumarin for acidic compounds . Acid chlorides such as dansyl chloride may also react with different functional groups carrying active hydrogens as do phenols. The use and development of new fluorescent probes in pharmaceutical analysis is a subject for further studies.

Journal Article↗