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Biomedical subjects

S Mudd

Publications and source records attributed to S Mudd.

At least 19 recordsLinked to original sources
PubMed2003

Identification of Lps2 as a key transducer of MyD88-independent TIR signalling.

In humans, ten Toll-like receptor (TLR) paralogues sense molecular components of microbes, initiating the production of cytokine mediators that create the inflammatory response. Using N-ethyl-N-nitrosourea, we induced a germline mutation called Lps2, which abolishes cytokine responses to double-stranded RNA and severely impairs responses to the endotoxin lipopolysaccharide (LPS), indicating that TLR3 and TLR4 might share a specific, proximal transducer. Here we identify the Lps2 mutation: a distal frameshift error in a Toll/interleukin-1 receptor/resistance (TIR) adaptor protein known as Trif or Ticam-1. Trif(Lps2) homozygotes are markedly resistant to the toxic effects of LPS, and are hypersusceptible to mouse cytomegalovirus, failing to produce type I interferons when infected. Compound homozygosity for mutations at Trif and MyD88 (a cytoplasmic TIR-domain-containing adaptor protein) loci ablates all responses to LPS, indicating that only two signalling pathways emanate from the LPS receptor. However, a Trif-independent cell population is detectable when Trif(Lps2) mutant macrophages are stimulated with LPS. This reveals that an alternative MyD88-dependent 'adaptor X' pathway is present in some, but not all, macrophages, and implies afferent immune specialization.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay.

Mutation screening in neurofibromatosis type 1 (NF1) families has long been hampered by the complexity of the NF1 gene. By using a novel multi-track screening strategy, 67 NF1 families (54 two-generation, 13 three-generation) with a de novo mutation in the germline of the first generation were studied with two extragenic and 11 intragenic markers. The pathological lesion was identified in 31 cases. Loss of heterozygosity (LOH) in the affected individual revealed a gross gene deletion in 15 of the two-generation families; in 12 (80%) of them, the deletion was maternally derived. Eleven patients with a gross deletion exhibited developmental delay, ten had dysmorphic features and six manifested a learning disability. No gross deletion was apparent in any of the 13 three-generation families, suggesting that such lesions are subject to more intense selection. In these families, the new mutation was of paternal origin in 11 kindreds and the underlying mutational event could be characterised in three of them.

Adolescent↗
PubMed1997

Program image ratings of a psychiatric facility as a measure of system performance.

The present study used in-patient psychiatric patient's ratings of 17 major elements of a hospital's programs. Previous work indicated that ratings by mental health staff of such elements were useful in discriminating quality among the services provided. Current work shows that patient ratings in such a facility show promising reliability and validity as measures of system performance and can thus be a valuable addition to the assessment and management of psychiatric services.

Analysis of Variance↗
PubMed1994

Severity and treatment of alcohol withdrawal in elderly versus younger patients.

We conducted a retrospective chart review of older (n = 48; mean age = 69) and younger (n = 36; mean age = 30) patients who were admitted to residential/inpatient treatment for alcohol withdrawal and dependence. Although the two age groups did not differ in terms of recent drinking history, the elderly group had significantly more withdrawal symptoms for a longer duration than the younger group. The elderly group also had more symptoms of cognitive impairment, daytime sleepiness, weakness, and high blood pressure. Finally, no significant differences were found between age groups in either the dosage or number of days of detoxification medication, although a trend was found for more days of medication in the elderly. We conclude that alcohol withdrawal may be more severe in elderly than in younger persons. Accordingly, treatment may take longer and should target the specific profile of symptoms that characterize alcohol withdrawal in the elderly.

Adult↗
PubMed1975

The effect of nonspecific immune stimulation on the recurrence rate of herpetic keratitis in rabbits.

Cellular immunity is of primary importance in resistance to virus infection. In this study, 75 rabbits were immunized with live BCG, 75 rabbits were immunized with Staphylococcus aureus, and 75 rabbits were injected with saline. Two weeks after immunization the corneal epithelium of both eyes was infected with McKrae strain herpes virus, and five weeks after immunization the rabbits were skin tested with old tuberculin or staphylococcus to ascertain their immune status. The corneas were observed under the slit lamp for recurrent epithelial herpes from day 52 through day 84 after immunization. During the second week of observation the group immunized with BCG had statistically significantly fewer recurrences than the saline-injected control group. The data for the BCG group during the remainder of the observation period, and for the SPL immunized group, were not statistically distinguishable from the control group. These experiments indicate that nonspecific immune stimulation provides little protection against recurrent herpetic infection. It is possible that manipulation of dosage and timing could enhance this effect.

Animals↗
PubMed1974

Specific and nonspecific cell-mediated resistance to influenza virus in mice.

We found that influenza virus had the capacity to replicate in the peritoneal macrophages of normal mice, as revealed by the development of hemadsorption and the appearance intracellularly of S and V antigens. Cell-mediated resistance was studied in mice infected with influenza virus or a bacterial sytem of induction-elicitation. In the homologous system, mice were injected intraperitoneally or exposed by aerosol to a sublethal dose of an egg-adapted swine strain of influenza virus. In the heterologous system, they were infected repeatedly with Staphylococcus aureus and elicited by subcutaneous or aerosol administration of staphylococcal antigens. The peritoneal macrophages from mice specifically or nonspecifically immunized were significantly more resistant than those from normal mice. Also longer survival to in vivo challenge by the mouse-adapted virus, as compared with normal mice, was indicated in bacterially stimulated mice.

Aerosols↗
PubMed1973

Lack of detectable circulating interferon in mice protected against vaccinia virus by induction and elicitation with bacterial systems.

Mice which had been subjected to mycobacterial infection and specific elicitation were bled from the orbital sinus at the time the mice were challenged intravenously with vaccinia virus. Assays of the sera were negative for interferon. Sera of rabbits sensitized with staphylococci and elicited by Staphage Lysate also lacked detectable circulating interferon.

Journal Article↗
PubMed1973

Protection of mice against vaccinia virus by bacterial infection and sustained stimulation with specific bacterial antigens.

In these experiments, mice which have a strong delayed-type hypersensitivity to mycobacteria were found, when elicited with old tuberculin, to be more resistant to intravenous vaccinia virus challenge than controls. This was manifest as protection from killing when large amounts of virus were injected, or as significantly less tail swelling and damage as well as lower titers of infectious virus when a lesser inoculum was used. Preliminary experiments indicate that animals sensitized with Staphylococcus aureus and elicited with phage lysate of staphylococcus are also more resistant to vaccinia infection.

Animals↗
PubMed1972

Staphylococcidal capability of rabbit peritoneal macrophages in relation to infection and elicitation: delayed-type hypersensitivity without increased resistance.

The staphylococcidal capability of populations of peritoneal macrophages in rabbits has been measured before and after repeated infections with Staphylococcus aureus. Such rabbits after infection showed delayed-type hypersensitivity to S. aureus antigens, but the staphylococcidal capability of the peritoneal macrophages was not increased. This result at the cellular level is in agreement with previous assessment in vivo of the consequences of staphylococcal infection. Pathways to cell-mediated resistance, with and without delayed-type hypersensitivity, are presented.

Animals↗
PubMed1972

Staphylococcidal capability of rabbit peritoneal macrophages in relation to infection and elicitation: induction and elicitation of activated macrophages.

The capability of macrophages to inactivate ingested staphylococci can be augmented when repeated infection is followed by specific elicitation with staphylococcal lysate. The increase in staphylococcidal capability with specific elicitation after infection is not dramatic but is statistically significant. The percentage of change in staphylococcidal capability after infection and specific elicitation is systematically related to the staphylococcidal capability of the populations of macrophages in the same rabbits studied prior to infection. When the capability of the initial populations of macrophages has been high, the percentage of change after infection and elicitation may be slight or even negative. When the staphylococcidal capability of the initial population of macrophages in a given rabbit has been low, there is typically a significant increase in this capability after infection and elicitation. It is shown at the cellular level that it is possible to evoke a population of activated macrophages, by a procedure which is analogous to procedures reported as useful in human practice.

Animals↗