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Biomedical subjects

T F Murphy

Publications and source records attributed to T F Murphy.

At least 109 records · Page 6Linked to original sources
PubMed1988

Nearest neighbor analysis of outer membrane proteins of nontypeable Haemophilus influenzae.

The arrangement of outer membrane proteins on the surface of nontypeable Haemophilus influenzae was investigated with cleavable and noncleavable bis-imidate cross-linking agents. Whole organisms were subjected to cross-linking agents, and oligomers of proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two-dimensional gel electrophoresis, and immunoblot assay, using monoclonal antibodies to outer membrane proteins. The major outer membrane protein (P2) formed dimers and trimers detected by all three methods. Oligomers of other outer membrane proteins were not detected. These data indicate that P2 exists as a trimer on the outer membrane and suggest that other outer membrane proteins exist as monomers on the outer membrane.

Antibodies, Monoclonal↗
PubMed1988

Purification and analysis with monoclonal antibodies of P2, the major outer membrane protein of nontypable Haemophilus influenzae.

The protein P2 comprises a large proportion of the outer membrane of nontypable Haemophilus influenzae and functions as a porin. In view of the importance of the protein as a surface antigen, the present study was designed to purify and analyze P2 with particular emphasis on detection of antigenic determinants expressed on the bacterial surface and identification of bactericidal targets on P2. The P2 protein was purified by using detergent solubility, anion-exchange chromatography, and gel-filtration chromatography sequentially. Two monoclonal antibodies to P2 were developed. One antibody (2E6) recognized a determinant expressed on the bacterial surface, whereas the other antibody (3F3) recognized an internal epitope. The surface-exposed 2E6 determinant was present on 12% of strains from a nationwide collection. P2 is a bactericidal target for antibody 2E6. Cyanogen bromide cleavage of P2 resulted in two fragments, as in type b strains. Both monoclonal antibodies recognized epitopes on the larger fragment. These observations have potentially important implications regarding the development of vaccines to prevent H. influenzae infections and the development of a serotyping system for epidemiologic studies.

Antibodies, Bacterial↗
PubMed1988

Is AIDS a just punishment?

There are religious and philosophical versions of the thesis that AIDS is a punishment for homosexual behaviour. It is argued here that the religious version is seriously incomplete. Because of this incompleteness and because of the indeterminacies that ordinarily attend religious argumentation, it is concluded that the claim may be set aside as unconvincing. Homosexual behaviour is then judged for its morality against utilitarian, deontological, and natural law theories of ethics. It is argued that such behaviour involves no impediment to important moral goals and is not therefore immoral. Where natural law might be used to condemn homosexual behaviour, it is argued that the theory itself is not well established. Consequently there is a prima facie reason for rejecting the philosophical version of the punishment thesis. This conclusion is further supported by noting the lack of proportion between the purported immorality of homosexuality and a punishment as devastating as AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cerebral infarction in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn and its attendant hypoxemia may place the infant at high risk for hypoxic-ischemic injury. In 19 infants with persistent pulmonary hypertension of the newborn, 16 of whom suffered intrapartum asphyxia, we evaluated a series of electroencephalograms (EEGs) for evidence of major focal cerebral injury, ie, persistent voltage attenuation and/or focal electrical-seizure activity. Of the 15 infants (78.9%) with such EEG findings, nine infants (47% of the total population) had cerebral infarction documented by cranial sonograms, computed tomographic scans, or autopsy findings. In eight (89%) of the nine infants with infarction, electrical seizures were noted during periods of muscle paralysis. We recommend (1) the use of electroencephalography in this population, particularly during periods of muscle paralysis, to detect underlying cerebrovascular lesions and (2) the use of cranial computed tomography if persistent, focal EEG abnormalities are noted.

Cerebral Infarction↗
PubMed1987

Outer membrane protein and lipooligosaccharide analysis of paired nasopharyngeal and middle ear isolates in otitis media due to nontypable Haemophilus influenzae: pathogenetic and epidemiological observations.

We studied isolates of nontypable Haemophilus influenzae from cultures of nasopharynx and middle ear fluid (MEF) done simultaneously on children with otitis media. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane protein (OMP) patterns demonstrated that in 16 of 19 pairs, the nasopharyngeal and MEF strains were identical. With four monoclonal antibodies to lipooligosaccharide (LOS) determinants, 17 of the 19 pairs were identical. Thus the pathogenesis of otitis media due to nontypable H. influenzae appears to involve spread of the bacteria from the nasopharynx to the middle ear. Analysis of middle ear isolates from four children with recurrent otitis media caused by nontypable H. influenzae indicated that the recurrent episodes were caused by reinfection with different strains rather than by persistence of the same strain. OMP and LOS analysis of strains from two sisters with concurrent otitis media suggested that person-to-person transmission of nontypable H. influenzae can occur among children.

Antibodies, Monoclonal↗
PubMed1987

Antigenic diversity of lipooligosaccharides of nontypable Haemophilus influenzae.

The lipooligosaccharides (LOS) of nontypable Haemophilus influenzae are an antigenically heterogeneous group of macromolecules. Immunodiffusion and enzyme-linked immunosorbent assay inhibition studies with phenol-water-extracted LOS and absorbed antisera specific for the oligosaccharide portion of the LOS identified six LOS strain-specific antigens. To facilitate screening large numbers of strains to search for LOS antigenic heterogeneity, a system utilizing proteinase K whole cell digests in Western blots was developed. Seventy-two nontypable H. influenzae LOS extracts were analyzed in this Western blot assay. Thirty-seven of these extracts could be segregated into 10 antigenically distinct LOS groups based on immunologic recognition by one or more of the rabbit antisera. Thirty-five of the strains did not contain these LOS antigens. These results demonstrate that antigenic differences exist among the LOS of nontypable H. influenzae strains, and this heterogeneity has the potential to be used to establish an LOS-based serogrouping system.

Antigens, Bacterial↗
PubMed1986

Evaluation of polylactic acid-carbon mesh for repair of ventral herniorrhaphy.

Large ventral hernias are a difficult surgical problem. Previous attempts to repair large defects in the abdominal wall with prostheses have been associated with recurrences and infection. A filamentous polylactic acid-carbon tissue mesh is a possible alternative prosthesis. We evaluated and compared polylactic acid-carbon mesh and Marlex mesh in repairing a large defect of the abdominal wall in a rat model. The polylactic acid-carbon mesh led to as strong a repair as Marlex mesh for the same time periods postoperatively; furthermore, no infection was noted with the former, whereas a 5.3 percent incidence of infection was noted with Marlex mesh. One mesh disruption was also noted with Marlex mesh. Polylactic acid-carbon mesh was found to have a more marked fibrotic response and a lesser inflammatory response. Polylactic acid-carbon mesh, therefore, appears to be more biocompatible, with more fibrosis, less inflammatory reaction, and equal strength to Marlex mesh. It is therefore a more appropriate synthetic material for a large ventral herniorrhaphy.

Abdominal Muscles↗
PubMed1986

A cure for aging?

Arthur Caplan has argued that the presumptive naturalness, universality, and inevitability of aging are no obstacles to conceptualizing aging as a disease since those traits are themselves merely contingent. Moreover, aging lends itself to discussion in terms of diagnostic symptomatology and etiology. Is aging therefore a disease? I argue that aging need not be shown to be unnatural or a disease in order to make it the subject of biomedical interest. I suggest that rather than ask "Is aging a disease?", the better point of philosophical departure would be to ask "Is aging objectionable such that its prevention and cure ought to be sought?". In this way, the moral issues at stake emerge more clearly. Chief among these issues are the potential results of curing aging and the implications for the prospect of meaningful human life without the de facto limitations that aging (and perhaps death) put upon it. A convincing argument that aging should be cured, therefore, would need to show that human significance warrants and possibly seeks such a cure and that the social costs of curing aging are morally acceptable.

Aging↗
PubMed1986

Antigenic characterization of the P6 protein of nontypable Haemophilus influenzae.

The purpose of this study was to characterize the degree of antigenic heterogeneity or conservation of a 16,600-dalton outer membrane protein (P6) among strains of nontypable Haemophilus influenzae. Immunization of rabbits with P6 isolated from individual strains resulted in antibody to P6 of all 25 strains tested. The titers of antibody in the sera were similar among the strains. Whole organisms of two strains were used to immunize rabbits, and antibodies were produced to P6 of all strains tested. Monoclonal antibodies developed to P6 from mice immunized with whole cells of three different strains recognized determinants on P6 of all 25 strains tested. Finally, pooled normal human serum contained antibodies to P6 of all 25 strains assayed. These studies indicate that P6 is a highly conserved antigen on the outer membrane of nontypable H. influenzae.

Animals↗
PubMed1986

Identification of a 16,600-dalton outer membrane protein on nontypeable Haemophilus influenzae as a target for human serum bactericidal antibody.

A 16,600-D outer membrane protein is present in all strains of Haemophilus influenzae and antibodies to this protein are present in human serum. This study was designed to assess the role of this outer membrane protein (P6) in nontypeable H. influenzae as a target for human serum bactericidal antibody. P6 was isolated and coupled to an affinity column. Depleting normal human serum of antibodies to P6 by affinity chromatography resulted in reduced bactericidal activity of that serum for nontypeable H. influenzae. Immunopurified antibodies to P6 from human serum were bactericidal. Finally, preincubation of bacteria with a monoclonal antibody that recognizes a surface epitope on P6, inhibited human serum bactericidal killing. Taken together, these experiments establish that P6 is a target for human bactericidal antibodies. This observation provides evidence that P6 plays a potentially important role in human immunity to infection by nontypeable H. influenzae.

Antibodies, Bacterial↗
PubMed1986

Biochemical and morphologic changes in hepatocytes from the shock injured liver.

It has been proposed that the isolated hepatocyte is an excellent model for the study of cellular changes during and after hemorrhagic shock. To investigate this proposition the biochemical and morphologic changes in the isolated hepatocyte of shock injured rats were documented. Use of the isolated hepatocyte allows direct measurement of intracellular biochemical changes which we find corroborates the results of basic shock studies done on rats using liver slices, perfused liver or specimens taken at biopsy. Morphologic changes in the shocked liver of the rat are noted using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The results are correlated with the biochemical changes. SEM of the isolated hepatocyte reveals marked swelling immediately after shock with some scattered blebs. The cells show some recovery at two hours with near complete normality restored at 24 hours. TEM of tissue and isolated cells reveal vacuolization and mitochondrial changes in the early post shock period with return to normality at 24 hours after shock. The shock injured hepatocyte is a reasonably faithful representative of the events which have taken place in the liver from which it is isolated. It can be used as a model for treatment in vivo or as a device for comparison of the effects of different environments in vivo or in vitro.

Adenine Nucleotides↗
PubMed1985

Functional and ultrastructural effects of nontypeable Haemophilus influenzae in a hamster trachea organ culture system.

A hamster trachea organ culture system was utilized to evaluate quantitatively the effects of a strain of nontypeable Haemophilus influenzae (NTHI) and culture supernatants of the same strain on ciliary activity. Tracheal explants were maintained in organ culture for 96 to 144 h and ciliary activity was observed daily with an inverted microscope. Explants continuously exposed to a strain of NTHI had a progressive decline in ciliary activity which was significantly lower than uninfected controls evaluated concomitantly by 48 h of exposure and thereafter. Histologic studies revealed a progressive degeneration of mucosal cells and exfoliation of ciliated cells. Scanning electron microscopy showed little adherence of NTHI to the mucosal surface. Sterile broth cultures of NTHI and supernatants of organ cultures infected with the same NTHI strain had no adverse effect on ciliary activity. Infected tracheal explants treated with ampicillin 24, 48, or 72 h after continuous bacterial challenge had no significant decline in ciliary activity compared to controls. The lack of adherence and the histologic changes observed when hamster trachea cultures were infected with NTHI suggested a toxin might mediate the damage observed. Broth and organ culture supernatants, however, produced no damage. Therefore, further studies are needed to determine the role, if any, of a toxin in the production of damage to hamster tracheal explants by NTHI.

Ampicillin↗
PubMed1985

Identification of a specific epitope of Haemophilus influenzae on a 16,600-dalton outer membrane protein.

A mouse monoclonal antibody that recognizes an epitope on a 16,600-dalton outer membrane protein was developed to nontypable Haemophilus influenzae. This epitope was present on all 115 isolates of H. influenzae tested, including typable and nontypable strains. Screening of 89 strains of other bacteria demonstrated that this epitope is a highly specific marker for H. influenzae because the epitope was absent in virtually all other bacterial species tested. Western blot assays were performed with two normal human serum samples and convalescent-phase serum from an adult with bacteremia due to nontypable H. influenzae. Antibody to the 16,600-dalton outer membrane protein was present in all three human serum samples.

Animals↗
PubMed1985

Antigenic heterogeneity of outer membrane proteins of nontypable Haemophilus influenzae is a basis for a serotyping system.

A serotyping system for nontypable Haemophilus influenzae (NTHI) was developed by using isolated outer membrane protein (OMP) preparations and rabbit antisera. OMPs of 23 strains were isolated by molecular sieve chromatography of outer membranes in 1.5% sodium deoxycholate buffer. These OMP preparations were relatively free of lipopolysaccharide as determined by silver staining of sodium dodecyl sulfate gels and by dot assay with a monoclonal antibody which is specific for the lipid A of H. influenzae. Three antisera raised to whole organisms were used to serotype 21 of 23 strains with a kinetic enzyme-linked immunosorbent assay. Digestion of OMP preparations with proteinase K removed greater than 90% of the antigenic reactivity, indicating that the system is based on OMP antigens. Marked antigenic heterogeneity of OMPs exists among strains of NTHI. By determining the pattern of serological reactivity of OMPs with the three antisera, isolates were divided into groups based on antigenic differences. Six serotypes were identified. This OMP serotyping system is based on multiple antigenic determinants. Future studies will focus on identifying serotype-specific epitopes to further refine this serological classification scheme for NTHI.

Antigens, Bacterial↗
PubMed1985

Antigenic heterogeneity of lipid A of Haemophilus influenzae.

The chemical structure and biologic function of the lipid A portion of lipopolysaccharide are not identical among gram-negative bacteria. This study indicates that antigenically heterogeneous lipid A exists among strains of Haemophilus influenzae. An immunoglobulin G3 murine monoclonal antibody, 3D2, produced against a nontypable H. influenzae strain 3524 has specificity for a site on the lipid A portion of the H. influenzae lipopolysaccharide. With the Western blot and immunodot assay, 3D2 recognized this lipid A determinant on 14 of 24 (58%) of strains of nontypable H. influenzae and in 51 of 95 (54%) strains of H. influenzae type b. This lipid A epitope has a high degree of specificity for H. influenzae, since it is not present on the lipid A of 39 gram-negative strains from 14 non-Haemophilus species. In addition, studies of 36 strains of six Haemophilus species other than H. influenzae and 8 strains of 4 species of Actinobacillus did not contain the 3D2 epitope. Enzyme-linked immunosorbent assay analysis with a kinetic assay and enzyme-linked immunosorbent assay inhibition confirmed the antigenic heterogeneity of H. influenzae lipid A. Thin-layer chromatography demonstrated that the 3D2 epitope is associated with a chloroform-soluble lipid moiety in the lipid A. Fluorescent antibody analysis of H. influenzae indicated that the epitope is on the cell surface. The monoclonal antibody was not bactericidal for strain 3524, and it did not inhibit the bactericidal action of normal human serum against the same strain. These studies demonstrate that the lipid As of H. influenzae are antigenically heterogeneous.

Antibodies, Monoclonal↗
PubMed1985

The moral significance of spontaneous abortion.

Spontaneous abortion is rarely addressed in moral evaluations of abortion. Indeed, 'abortion' is virtually always taken to mean only induced abortion. After a brief review of medical aspects of spontaneous abortion, I attempt to articulate the moral implications of spontaneous abortion for the two poles of the abortion debate, the strong pro-abortion and the strong anti-abortion positions. I claim that spontaneous abortion has no moral relevance for strict pro-abortion positions but that the high incidence of spontaneous abortion is not (as some claim) eo ipso any sort of justification for voluntarily induced abortion. Secondly, I show that if the strict anti-abortionist position is to be taken seriously in its insistence that prenatal life has a right to be protected by virtue of its being conceived, then it seems necessary to take measures to prevent spontaneous abortion and its presumptive causes, and this as a matter of moral obligation.

Abortion, Spontaneous↗