Absence of an association between HLA-DRB1*04 and rheumatoid arthritis in newly diagnosed cases from the community.

OBJECTIVES--To determine HLA-DR4 and DR1 allele frequencies in a series of patients with newly diagnosed early inflammatory arthritis. METHODS--HLA-DR1 and DR4 frequencies were determined by oligonucleotide typing of 208 patients classified as having either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis. RESULTS--The frequency of occurrence of DR4 in these patients with RA did not differ significantly from that in controls in the United Kingdom (42 v 37%). HLA-DR1 was increased in the group with inflammatory polyarthritis (25 v 18%). CONCLUSIONS--The frequency of DR4 is not increased in newly diagnosed community based patients with RA. This supports the hypothesis that DR4 is less important as a marker for susceptibility to RA than it is for disease persistence or severity.     

Can a Single Muscle Fiber Model the Features of Myocardial Stunning?

The exact mechanisms that cause myocardial stunning are still unclear. We previously utilized a computer model of the ventricle that was effective in modeling the dominant observable features of stunning, but it was not simple to implement. This led to the design of a single muscle fiber model. The mathematical model of a muscle fiber consisted of three elements: a contractile element, a series elastic element, and a parallel elastic element. The model created length waveforms based on time-dependent force and contractile stiffness functions. This model was initially evaluated by entering the same regional parameter values used in the global dual region ventricular model. First a reduction of the contractile stiffness function was applied by reducing the peak stiffness by 30%, and then the rates of activation and deactivation were reduced by 20% while maintaining the peak values constant. The three-element model produced results very similar to the canine and ventricular model. Thus, it is concluded that the simpler three-element model provides an accurate model of the myocardial tissue and its deficiencies during stunning.     

A nuclear mutant of Chlamydomonas that exhibits increased sensitivity to UV irradiation,reduced recombination of nuclear genes,and altered transmission of chloroplast genes

Summary Meiotic progeny of Chlamydomonas reinhardtii normally receive chloroplast genomes only from the mt ⁺ parent. However, exceptional zygotes, which transmit the chloroplast genomes of both parents or, more rarely, only those of the mt ^- parent, arise at a low frequency. Mutations at the mt ⁺-linked mat-3 locus were found previously to elevate the transmission of chloroplast genomes from the mt-parent, resulting in a much higher than normal frequency of exceptional zygotes. In this paper we demonstrate that an ultraviolet-sensitive nuclear mutation mapping at the uvsE1 locus, which is unlinked to mating type, also promotes chloroplast genome transmission from the mt ^- parent. This mutant, which was previously shown to reduce recombination of nuclear genes in meiosis, acts synergistically which the mat3-3 mutation to produce an extremely high frequency of exceptional zygotes. Through the use of restriction fragment length polymorphisms existing in the chloroplast genomes of C. reinhardtii and the interfertile strain C. smithii, we show that chloroplast DNA fragments from the mt ^- parent normally begin to disappear shortly after zygote formation. However, this process appears to be blocked totally in the absence of wild-type uvsE1 and mat-3 gene products. Our findings are consistent with the hypothesis that both gene products contribute to the mechanism responsible for uniparental inheritance of the chloroplast genome from the mt ⁺ parent.