Biomedical subjects

Paul Hyman

Publications and source records attributed to Paul Hyman.

4 recordsLinked to original sources

PubMed2004

Chronic pain in individuals with previously undiagnosed autistic spectrum disorders.

UNLABELLED: The aim of this article is to heighten clinician awareness by describing 2 patients with signs and symptoms of a possible autistic disorder. Autistic spectrum disorders are neurodevelopmental disorders characterized by impairment in reciprocal social interaction skills or communication skills and/or by the presence of stereotyped behavior, interests, and activities. Pain can be the initial presenting symptom for individuals with a previously undiagnosed autistic spectrum disorder. Two case presentations show indicators, such as reported sensory abnormalities, impaired social behaviors, and unusual interests, that should lead the physician to consider a referral for further evaluation. An accurate diagnosis of autism or related disorder can lead to a greater understanding of the nature of the patient's pain, as well as to more appropriate and effective treatment strategies. In addition, such patients might benefit from therapeutic interventions to improve overall functioning and decrease distress and, consequently, to decrease pain and other symptoms. Finally, autism research might inform pain researchers on topics such as neurobiology, development, and treatment of chronic pain disorders. PERSPECTIVE: Pain experts might be underrecognizing signs and symptoms of autistic spectrum disorders (ASDs) in their patients. Clinical evaluation for ASDs should be considered in patients with specific unusual characteristics. Research on the topic of ASDs and pain is encouraged.

Adolescent↗

PubMed2004

In vivo bypass of chaperone by extended coiled-coil motif in T4 tail fiber.

The distal-half tail fiber of bacteriophage T4 is made of three gene products: trimeric gp36 and gp37 and monomeric gp35. Chaperone P38 is normally required for folding gp37 peptides into a P37 trimer; however, a temperature-sensitive mutation in T4 (ts3813) that suppresses this requirement at 30 degrees C but not at 42 degrees C was found in gene 37 (R. J. Bishop and W. B. Wood, Virology 72:244-254, 1976). Sequencing of the temperature-sensitive mutant revealed a 21-bp duplication of wild-type gene 37 inserted into its C-terminal portion (S. Hashemolhosseini et al., J. Mol. Biol. 241:524-533, 1994). We noticed that the 21-amino-acid segment encompassing this duplication in the ts3813 mutant has a sequence typical of a coiled coil and hypothesized that its extension would relieve the temperature sensitivity of the ts3813 mutation. To test our hypothesis, we crossed the T4 ts3813 mutant with a plasmid encoding an engineered pentaheptad coiled coil. Each of the six mutants that we examined retained two amber mutations in gene 38 and had a different coiled-coil sequence varying from three to five heptads. While the sequences varied, all maintained the heptad-repeating coiled-coil motif and produced plaques at up to 50 degrees C. This finding strongly suggests that the coiled-coil motif is a critical factor in the folding of gp37. The presence of a terminal coiled-coil-like sequence in the tail fiber genes of 17 additional T-even phages implies the conservation of this mechanism. The increased melting temperature should be useful for "clamps" to initiate the folding of trimeric beta-helices in vitro and as an in vivo screen to identify, sequence, and characterize trimeric coiled coils.

Amino Acid Sequence↗

PubMed2003

Experimental examination of bacteriophage latent-period evolution as a response to bacterial availability.

For obligately lytic bacteriophage (phage) a trade-off exists between fecundity (burst size) and latent period (a component of generation time). This trade-off occurs because release of phage progeny from infected bacteria coincides with destruction of the machinery necessary to produce more phage progeny. Here we employ phage mutants to explore issues of phage latent-period evolution as a function of the density of phage-susceptible bacteria. Theory suggests that higher bacterial densities should select for shorter phage latent periods. Consistently, we have found that higher host densities (>/== approximately 10(7) bacteria/ml) can enrich stocks of phage RB69 for variants that display shorter latent periods than the wild type. One such variant, dubbed sta5, displays a latent period that is approximately 70 to 80% of that of the wild type-which is nearly as short as the RB69 eclipse period-and which has a corresponding burst size that is approximately 30% of that of the wild type. We show that at higher host densities (>/== approximately 10(7) bacteria/ml) the sta5 phage can outcompete the RB69 wild type, though only under conditions of direct (same-culture) competition. We interpret this advantage as corresponding to slightly faster sta5 population growth, resulting in multifold increases in mutant frequency during same-culture growth. The sta5 advantage is lost, however, given indirect (different-culture) competition between the wild type and mutant or given same-culture competition but at lower densities of phage-susceptible bacteria (</= approximately 10(6) bacteria/ml). From these observations we suggest that phage displaying very short latent periods may be viewed as specialists for propagation when bacteria within cultures are highly prevalent and transmission between cultures is easily accomplished.

Amino Acid Sequence↗

PubMed2002

Design of protein struts for self-assembling nanoconstructs.

Bacteriophage T4 tail fibers have a quaternary structure of bent rigid rods, 3 x 160 nm in size. The four proteins which make up these organelles are able to self-assemble in an essentially irreversible manner. To use the self-assembly domains of these proteins as elements in construction of mesoscale structures, we must be able to rearrange these domains without affecting the self-assembly properties and add internal binding sites for other functional elements. Here we present results on several alterations of the P37 component of the T4 tail fiber that change its length and add novel protein sequences into the protein. One of these sequences is an antibody binding site that is used to inactivate phage carrying the modified gene.

Adsorption↗