Biomedical subjects

N L Martin

Publications and source records attributed to N L Martin.

At least 37 records · Page 2Linked to original sources

PubMed1993

Serum levels of soluble CD8, neopterin, beta 2-microglobulin and p24 antigen as indicators of disease progression in children with AIDS on zidovudine therapy.

OBJECTIVE: To test the hypothesis that serum levels of soluble markers in children change after initiation of zidovudine therapy and that the extent and pattern of these longitudinal changes correlates with clinical outcome. PATIENTS AND METHODS: We measured serum levels of soluble CD8, neopterin, beta 2-microglobulin (beta 2M), and p24 antigen, and CD4 cell counts, before the initiation of zidovudine therapy and at 12, 24 and 48 weeks of treatment in 24 HIV-1-infected children (Centers for Disease Control classification P2) and 15 controls. RESULTS: Soluble CD8 levels were elevated before therapy in 70% of the infected children; subsequent decreases were associated with lower risk of disease progression. The mean serum neopterin level before treatment was elevated in infected children; decreases in neopterin levels marginally reflected improved or stable clinical status. Serum beta 2M levels and CD4+ cell counts were not associated with clinical outcome. Only 10 out of the 24 patients had detectable levels of serum p24 antigen before treatment; again, the amount of decline after initiation of therapy did not predict clinical outcome. CONCLUSION: Decreasing levels of soluble CD8 and neopterin in HIV-1-infected children receiving zidovudine therapy might reflect a good response to treatment and a slowing of disease progression.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Musculoskeletal manifestations of chronic renal insufficiency.

Abnormalities involving the musculoskeletal system are numerous and frequent in patients with chronic renal insufficiency (CRI). The most common radiologic manifestations of CRI are those referred to collectively as renal osteodystrophy: the findings seen in secondary hyperparathyroidism (bone resorption, periosteal reaction, and brown tumors), osteoporosis, osteosclerosis, osteomalacia, and soft-tissue and vascular calcification. Bone resorption, the most frequent alteration of CRI, occurs in several locations (subperiosteal, subchondral, trabecular, endosteal, and subligamentous), whereas brown tumors and periosteal reaction are much less common. Osteosclerosis primarily affects the axial skeleton and may be the only sign of CRI. Osteoporosis and osteomalacia cause osteopenia and are not infrequent changes of CRI. The prevalence of calcifications increases with the duration of hemodialysis. The other major group of musculoskeletal abnormalities attributable to CRI includes aluminum deposition, amyloid deposition and destructive spondyloarthropathy, tendon rupture, crystal deposition, infection, and avascular necrosis. These changes are less common than those of renal osteodystrophy and are more frequently seen in patients who have undergone long-term hemodialysis or renal transplantation. Recognition of musculoskeletal manifestations is important in the clinical management of patients with CRI.

Bone Diseases↗

PubMed1992

Low number of antibody producing cells in patients with sickle cell anemia.

B cell function is impaired in patients with sickle cell anemia. Although the number of surface IgM positive cells was similar in sickle cell patients and controls, in vitro spontaneous IgM, and PWM stimulated IgA, IgM, and IgG synthesis was significantly lower in the patients than in controls. The number of PWM induced and antigen specific immunoglobulin producing cells after immunization with Pneumovax, containing 21 serotypes of Streptococcus pneumoniae, was about 100-fold lower in the patients as compared with controls. Finally, the ability of the patients' peripheral blood mononuclear cells to proliferate in response to mitogens (PWM, SAC, PHA) was diminished. Because of the observed impairments in both nonspecific and antigen specific immunoglobulin synthesis and cell proliferation assays in the patients, we determined serum concentrations of IL-4 and IL-6, two cytokines associated with antibody production. IL-4 concentrations appeared low in sickle cell patients, and correlated with that of serum IgM. We hypothesize that B cell maturation in sickle cell patients is arrested at an IL-4 dependent stage.

Adult↗

PubMed1992

Analysis of the Pseudomonas aeruginosa major outer membrane protein OprF by use of truncated OprF derivatives and monoclonal antibodies.

TnphoA mutagenesis of the cloned oprF gene was utilized to generate 16 classes of fusions encoding differing lengths of the amino terminus of OprF fused to either alkaline phosphatase or to peptide tags of 1 to 20 amino acids, depending on the orientation and reading frame into which TnphoA was inserted. Representatives of each of the 16 classes were sequenced to determine the precise fusion joint. Four of these 16 representatives which produced in-frame fusions to alkaline phosphatase and another 8 with fusion joints in the amino-terminal half of OprF failed to react with a panel of 10 specific monoclonal antibodies. In contrast, OprF derivatives with predicted fusion joints at amino acids 180, 204, 289, and 299 reacted with one to five of the monoclonal antibodies. Four other immunoreactive OprF derivatives were created by subcloning and encoded amino acids 1 to 187, 188 to 326, 1 to 273 and 1 to 170 plus 301 to 326. On the basis of reactivity with the TnphoA-truncated derivatives and subclones of oprF, the epitopes for all 10 monoclonal antibodies were localized, in part, to specific regions of OprF. Nine of the 10 monoclonal antibodies, 8 of which recognize surface-exposed epitopes, mapped within the carboxy-terminal region of OprF that is homologous to the Escherichia coli outer membrane protein OmpA. Thus, we concluded that parts of the carboxy terminus of OprF are exposed on the external face of the outer membrane. In addition, a clone containing only the first two cysteine residues of OprF demonstrated reactivity with monoclonal antibodies MA4-4 and MA7-8 that was destroyed by 2-mercaptoethanol treatment, as was reactivity with intact OprF. Thus, we conclude that this first pair of cysteines at residues 176 and 185 of mature OprF form a disulfide bond.

Antibodies, Monoclonal↗

PubMed1992

Reevaluation, using intact cells, of the exclusion limit and role of porin OprF in Pseudomonas aeruginosa outer membrane permeability.

Earlier studies that used model membrane reconstitution methods have come to different conclusions regarding the exclusion limit of the outer membrane of Pseudomonas aeruginosa and whether OprF is the major channel-forming protein in the outer membrane. In this study, a 6.2-kbp SalI fragment, encoding only two cytoplasmic enzymes, alpha-galactosidase and sucrose hydrolase, and the inner membrane raffinose permease, was cloned behind the m-toluate-inducible tol promoter of vector pNM185 to create plasmid pFB71. P. aeruginosa strains harboring pFB71, when grown with inducer, produced both enzymes encoded by the insert and had acquired the ability to grow on the disaccharide melibiose and the trisaccharide raffinose. The rate of growth was dependent on the concentration and size of the saccharide and was decreased three- to fivefold by the absence of OprF, as examined by measuring the growth on melibiose and raffinose of an isogenic OprF-deficient omega insertion derivative, H636(pFB71). At high concentrations, di-, tri-, and tetrasaccharides could pass across the outer membrane to plasmolyze P. aeruginosa, as measured by light scattering and confirmed by electron microscopy. The initial rate kinetics of light-scattering changes were dependent on the size of the saccharide being used. Furthermore, the rates of change in light scattering due to raffinose and stachyose uptake across the outer membrane for strain H636 were fivefold or more lower than for its OprF-sufficient parent H103. These data are consistent with model membrane studies showing that OprF is the most predominant porin for compounds larger than disaccharides in P. aeruginosa and suggest that the exclusion limit for this porin and the outer membrane is greater than the size of a tetrasaccharide. In addition, these data confirmed the existence of other porins with a predominant function in monosaccharide uptake and a more minor function in the uptake of larger saccharides.

Bacterial Outer Membrane Proteins↗

PubMed1992

Computed radiography in musculoskeletal imaging: state of the art.

Computed radiography is a 2K x 2K x 10 bit digital radiographic system that replaces the film-screen combination with a photo-stimulable phosphor plate. The advantages of this relatively new technology include linear detector response, improved detector efficiency, and digital processing capabilities. Musculoskeletal applications benefit significantly from these attributes, which result clinically in the ability to reduce both radiation dose and number of exposures. Studies of observers' performance have shown no statistically significant difference in diagnostic accuracy between film-screen and computed radiographic musculoskeletal images. Computed radiography is particularly useful in the evaluation of the musculoskeletal system in traumatized patients with portable radiographs, spine radiographs, scoliosis studies, and depiction of soft-tissue abnormalities. Limitations include change in image format and size, high cost, decreased spatial resolution, restricted throughput, increased perception of noise, and new artifacts that must be recognized. Spatial resolution limitations of computed radiography in identification of fine detail information can be improved by using magnification techniques. Radiation dose reduction with an exposure decrease of 25-50% can be achieved without loss of diagnostic accuracy, although this depends on the examination and the abnormality. An interactive workstation is important in the use of a computed radiographic system with capabilities to adjust display parameters to best depict images and disease. We conclude that computed radiography is an alternative to film-screen radiography without significant differences in diagnostic quality in the evaluation of musculoskeletal images.

Humans↗

PubMed1992

A screening test for the detection of anti-HIV-1 IgA in young infants.

A simple dot blot screening test for anti-HIV-1 IgA in infant sera was developed using recombinant HIV proteins. Ten control infants, 19 uninfected infants of seropositive mothers and 12 HIV culture positive infants were studied at 3 month and 18 month time points. Prior to IgG depletion of the serum samples, 11/12 (92%) of the infected infants, 2/19 (11%) of the uninfected and none of the control infants were anti-HIV IgA positive at 3 months of age. After depletion, no anti-HIV IgA antibodies could be detected in the samples from uninfected infants, whereas the antibodies persisted in all 11 samples from the infected infants, resulting in sensitivity and specificity of 91.7% (95% confidence limits 59.8-99.6%) and 100% (79.1-100%) respectively. The assay might prove useful in the early diagnosis of HIV infection and can be performed at a fraction of the cost of commercially available western blot strips.

HIV Antibodies↗

PubMed1991

Detection of infection with human immunodeficiency virus (HIV) type 1 in infants by an anti-HIV immunoglobulin A assay using recombinant proteins.

To diagnose infection with the human immunodeficiency virus (HIV) soon after birth in infants born to HIV type 1-infected women, we developed antiviral IgA Western blot and dot blot assays with recombinant HIV-1 proteins. Thirty-three infants born to HIV-1-seropositive mothers and nine infants born to HIV-1-seronegative intravenous drug-abusing mothers were followed prospectively. Infection was documented by positive virus culture. Results with the polymerase chain reaction were used for comparison. Twelve infants were found infected with HIV-1; the earliest age at which cultures became positive ranged from birth to 31 weeks of age. Of the 12 culture-positive infants, 10 had anti-HIV IgA antibodies detectable initially between birth (cord blood) and 27 weeks of age. Anti-HIV IgA was not present in the uninfected infants or in the control subjects, either by Western blot or dot blot assays. Testing for anti-HIV IgA antibodies with recombinant HIV-1 proteins is an effective method for detecting viral infection in newborn and young infants.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Serum interleukin-6 concentrations are elevated and associated with elevated tumor necrosis factor-alpha and immunoglobulin G and A concentrations in children with HIV infection.

Hypergammaglobulinemia is one of the most consistent, and usually the first observable abnormality in infants vertically infected with HIV. We have analyzed serum interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)-alpha, and immunoglobulin (Ig) concentrations in 23 HIV-infected and 21 uninfected children. IL-6 and TNF-alpha concentrations in HIV-infected children were significantly higher than those in uninfected children, and mutually correlated. No differences in serum IL-4 levels between infected and uninfected children were observed. There was a correlation between serum IL-6 and IgG and between IL-6 and IgA concentrations. Furthermore, during follow-up changes in IL-6 levels were usually accompanied by corresponding changes in IgG levels. Our data indicate an association between HIV, IL-6, TNF-alpha and hypergammaglobulinemia. Regardless of the source and initial stimulus, continued production of IL-6 and TNF-alpha may result in augmentation in an auto-feedback manner, accompanied by increases in Ig synthesis and, more importantly, HIV replication. Thus, elucidation of the mechanisms responsible for overproduction of these two cytokines in HIV-infected patients is not only interesting from a biologic point of view, but is likely to have important clinical implications as well.

B-Lymphocytes↗

PubMed1990

Sequence and relatedness in other bacteria of the Pseudomonas aeruginosa oprP gene coding for the phosphate-specific porin P.

The oprP gene encoding the Pseudomonas aeruginosa phosphate-specific outer membrane porin protein OprP was sequenced. Comparison of the derived amino acid sequence with the known sequences of other bacterial porins demonstrated that OprP could be no better aligned to these porin sequences than it could to the periplasmic phosphate-binding protein PhoS of Escherichia coli. Southern hybridization and restriction mapping of the oprP gene in 37 clinical isolates and the 17 serotype strains of P. aeruginosa revealed that restriction sites in the vicinity of the oprP gene were highly conserved. Several species from the Pseudomonas fluorescens rRNA homology group contained DNA that hybridized to an oprP gene probe.

Amino Acid Sequence↗

PubMed1990

Nondisplaced fractures: spatial resolution requirements for detection with digital skeletal imaging.

Fifty-six radiographs of nondisplaced or minimally displaced fractures of the extremities and an equal number of studies with normal findings were selected and digitized to produce spatial resolution varying from 5.75 to 0.72 line pairs per millimeter (1p/mm), corresponding to pixel sizes ranging from 0.08 to 0.64 mm. The conventional and digitized images were evaluated by 10 radiologists, who gave their decision confidence on a graded scale. Receiver operating characteristic analyses were performed from these data to compare the digital images with the conventional radiographs. There was a progressive improvement in observer performance as the pixel size decreased. A pixel size greater than 0.16 mm (2.88 1p/mm) resulted in a significant loss of diagnostic accuracy in comparison with conventional radiographs. Specific fractures in which a larger pixel size adversely affected the evaluation included torus injuries, corner fractures in child abuse, minimal avulsion injuries, and fractures that demonstrated only trabecular disruption.

Adult↗

PubMed1989

Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone.

Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

Bone Neoplasms↗

PubMed1989

Image data compression in magnification hand radiographs.

A study was conducted on the use of an irreversible compression technique, Fourier quantization, to reduce the amount of digital data needed for an image. The effect of image compression was studied in radiographs obtained to diagnose subperiosteal bone resorption. Magnification radiographs of 44 hands were digitized to an array size of 4,096 X 4,096 X 12 bits. Selected subregions containing a single middle phalanx were compressed and reconstructed. A subset of the resultant 12-bit uncompressed and 8-, 7-, and 6-bit compressed images were read by four radiologists whose responses were analyzed with receiver operating characteristic (ROC) techniques. There were 81 images used in the ROC analysis, of which 48 were normal and 33 showed subperiosteal resorption. No statistically significant loss of diagnostic quality was detected for 8- or 7-bit compressed images, with average compression ratios of 16:1 and 28:1, respectively. Diagnostic quality was lost with 6-bit images, with an average compression ratio of 107:1.

Arthritis↗

PubMed1989

A report-coding system for integration into a digital radiology department.

Report-coding systems allow the radiologist to generate a typewritten radiographic report with a computer. Typically, the report is generated by selecting bar codes, speaking key words, or selecting items on a screen. MAMM REPORT is a report-coding system for mammography, developed by radiologists, that runs on a microcomputer (Amiga, Commodore Co., West Chester, PA). MAMM REPORT speaks questions to the radiologist, who responds by pressing one of two buttons on a computer mouse, thus generating the report. MAMM REPORT allows labeling of digital images and reduction of data required to store the report in computer memory (data compression). Data compression is useful for improving computer operating speed. Digital image labeling and data compression facilitate use of MAMM REPORT on a future digital radiology workstation for an all-digital radiology department. Sixty mammographic reports, reviewed by a radiologist who is not a specialist in mammography, were entered into MAMM REPORT. The mammography specialists who dictated the original reports then judged whether the reports generated by MAMM REPORT would be acceptable replacements on the basis of descriptions of findings, diagnoses, and recommendations for further study. Data compression was measured by calculating the ratio of the number of bytes for storage of the reports in original form to a standard storage form (Huffman encoding) and to the MAMM REPORT coded form. All 60 coded reports were acceptable replacements for the original reports. For computer storage, MAMM REPORT produced a compression ratio of 135 to 1 and Huffman encoding, 1.1 to 1. Huffman encoding did not compress most reports because of their brevity. The results indicate that report coding can produce data compression of radiographic reports. The standard method of text storage, Huffman encoding, is not suitable for application to mammographic reports, which tend to be brief.

Electronic Data Processing↗

PubMed1988

Large-scale purification and biochemical characterization of crystallization-grade porin protein P from Pseudomonas aeruginosa.

A large-scale purification scheme was developed for lipopolysaccharide-free protein P, the phosphate-starvation-inducible outer-membrane porin from Pseudomonas aeruginosa. This highly purified protein P was used to successfully form hexagonal crystals in the presence of n-octyl-beta-glucopyranoside. Amino-acid analysis indicated that protein P had a similar composition to other bacterial outer membrane proteins, containing a high percentage (50%) of hydrophilic residues. The amino-terminal sequence of this protein, although not homologous to either outer membrane protein, PhoE or OmpF, of Escherichia coli, was found to have an analogous protein-folding pattern. Protein P in the native trimer form was capable of maintaining a stable functional trimer after proteinase cleavage. This suggested the existence of a strongly associated tertiary and quaternary structure. Circular dichroism studies confirmed these results in that a large proportion of the protein structure was determined to be beta-sheet and resistant to acid pH and heating in 0.1% sodium dodecyl sulphate.

Amino Acid Sequence↗

PubMed1988

Interaction of macrophage cationic proteins with the outer membrane of Pseudomonas aeruginosa.

The interaction of the polycationic rabbit alveolar macrophage cationic proteins MCP-1 and MCP-2 (or their identical neutrophil equivalents NP-1 and NP-2) with the surface of Pseudomonas aeruginosa was investigated. Both proteins bound avidly to purified lipopolysaccharide, as judged by their ability to competitively displace the probe dansyl polymyxin with 50% inhibition (I50) values of 2 to 3 microM. Similar I50 were measured with dansyl polymyxin as a probe for cell surface binding, suggesting that the initial binding site for MCP-1 and MCP-2 on the surface of cells was lipopolysaccharide. Both MCP-1 and MCP-2 permeabilized outer membranes to the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN). The initial rate of NPN uptake plotted against the concentration of MCP-1 or MCP-2 gave sigmoidal curves, suggesting cooperative permeabilization of the outer membrane. Replotting the data as a Hill plot gave an affinity parameter, S0.5, the concentration of MCP giving a half-maximal increase in the rate of NPN uptake, of 5 and 25 microM for MCP-1 and MCP-2, respectively, and thus subsequent studies concentrated on the more active permeabilizer MCP-1. Permeabilization of outer membranes to NPN was a function of buffer pH, with lower pH considerably favoring the permeabilizing effects of MCP-1. Thin-section electron microscopic visualization of MCP-1-treated cells showed production of extended blebs. Further evidence of an altered cell surface after MCP-1 treatment was obtained by demonstrating that treated unopsonized cells were more efficiently phagocytosed by unelicited rabbit alveolar macrophages. The data overall suggest that macrophage cationic proteins interact with the P. aeruginosa outer membrane in a manner typical of other polycations and suggest that one of their major functions may be to permeabilize the outer membrane.

Antimicrobial Cationic Peptides↗

PubMed1987

Tumor necrosis factors alpha and beta in acquired immunodeficiency syndrome (AIDS) and aids-related complex.

Human immunodeficiency virus (HIV) infection is associated with abnormalities of both T-cell and B-cell immunity in patients with acquired immunodeficiency syndrome (AIDS). Previous studies demonstrated deficient production of the cytokines interleukin-1 (IL-1), interleukin-2 (IL-2), and gamma interferon (IFN-gamma). Tumor necrosis factor alpha and tumor necrosis factor beta have not been previously investigated in AIDS. In this study we demonstrate that peripheral blood mononuclear cells from patients with HIV infection who have either AIDS-related complex or acquired immunodeficiency syndrome are deficient in the production of tumor necrosis factor alpha and tumor necrosis factor beta. These cytokines, derived predominantly from monocytes or lymphocytes, respectively, function as immunoregulatory, antitumor, and antiinfective proteins. A deficiency in their production may therefore be responsible for many of the complications associated with HIV infection in patients with AIDS-related complex or acquired immunodeficiency syndrome.

AIDS-Related Complex↗

PubMed1987

Treatment of metastatic bone pain with strontium-89.

We have utilized 89Sr as palliative treatment for bone pain secondary to metastatic cancer in the skeleton of over 200 patients. The best results have been in patients with carcinoma of the prostate (80% response rate) and breast (89%). Results in a small number of patients with a variety of other cell types were not nearly as encouraging. Strontium-89 provides excellent palliation in the management of bone pain secondary to prostate and breast carcinoma.

Adolescent↗