Evidence that Lyb-5 is a differentiation antigen in normal and xid mice

These studies addressed the question of whether the Lyb-5 determinant on mouse B cells might represent a marker for a unique lineage of B cells as has been thought, or rather, a differentiation antigen. Previous studies have addressed this question by treating splenic B cells with anti-Lyb-5 + complement and then culturing them with various antigens. In this study, we first immunized in vivo or in vitro and then determined susceptibility to anti-Lyb-5. These studies demonstrate that a substantial proportion of antibody-forming cells produced in response to immunization with sheep red blood cells, trinitrophenyl (TNP)-keyhole limpet hemocyanin, TNP-Brucella abortus, TNP-lipopolysaccharide, as well as TNP-Ficoll, are eliminated by anti-Lyb-5 + complement treatment at the end of culture. Some generation of Lyb-5+ antibody-forming cells occurred in the last 24 hr of culture. These studies suggest that the Lyb-5 marker represents a differentiation antigen on relatively mature B cells.     

Immunological studies of Escherichia coli mutants lacking one or two ribosomal proteins

Summary A battery of immunological tests were used to investigate mutants which had been determined as lacking one or two ribosomal proteins on the basis of two-dimensional polyacrylamide gels. Proteins which were confirmed as missing from the ribosome in one or more mutants were large subunit proteins L1, L15, L19, L24, L27, L28, L30 and L33 and small subunit proteins S1, S9, S17 and S20. Cross-reacting material (CRM) was also absent from the post-ribosomal supernatant except in the case of protein S1. Since mutants lacking protein L11 have been previously described, any one of 13 of the 52 ribosomal proteins can be missing. None of these 13 proteins, except S1, can therefore have an indispensable role in ribosome function or assembly. In several mutants in which a protein was not missing but altered, it was present as several moieties of differing charge and size.     

Immunocytochemical Quantification of Tyrosine Hydroxylase at a Cellular Level in the Mesencephalon of Control Subjects and Patients with Parkinson's and Alzheimer's Disease

Abstract: Parkinson's disease is characterized by massive degeneration of the melanized dopaminergic neurons in the substantia nigra. The functional capacity of the surviving nigral neurons is affected, as indicated by the subnormal levels of tyrosine hydroxylase (TH) mRNA in these neurons and the presence in the parkinsonian mesencephalon of melanized neurons lacking TH immunoreactivity. This is apparently in contradiction with the known overactivity of dopamine synthesis and release that occurs in the remaining dopaminergic terminals. To test the ability of the surviving neurons to express TH protein, a semiquantitative immunocytochemical method was developed. The relative amounts of TH were estimated with a computer-assisted image analysis system in the dopaminergic neurons of representative mesencephalic sections of control and parkinsonian brains and for comparison in brains from patients with Alzheimer's disease. In control brains, the mean TH content per neuron differed from one subject to another and between the different dopaminergic cell groups of the mesencephalon in the same subject. Within a given dopaminergic region, the level of TH was variable among neurons. In patients with Parkinson's disease, the ratio of TH protein content per neuron in the substantia nigra by reference to that of the central gray substance was reduced. In patients with Alzheimer's disease, the amount of TH was selectively reduced in the remaining dopaminergic neurons of the ventral tegmental area, a region characterized by a loss in dopaminergic neurons. The decrease in cellular TH content might therefore be related to the presence of the neurodegenerative process in the area considered. In patients with Parkinson's disease, the incapacity of the surviving neurons to express normal TH levels may reduce the efficiency of the hyperactivity mechanisms that develop in the remaining striatal dopaminergic terminals.     

Familial mediterranean fever (FMF) in Moroccan Jews: Demonstration of a founder effect by extended haplotype analysis

Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated “MEF”) is on 16p, with the gene order 16cen–D16S80–MEF–D16S94–D16S283–D16S291–16pter. Here we report the association of FMF susceptibility with alleles at D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families (14 Moroccan, 17 non-Moroccan). We observed highly significant associations at D16S283 and D16S291 among the Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94–D16S283–D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lower haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics.     

Mutations in the SLC3A1 Transporter Gene in Cystinuria

Cystinuria is an autosomal recessive disease characterized by the development of kidney stones. Guided by the identification of the SLC3A1 amino acid–transport gene on chromosome 2, we recently established genetic linkage of cystinuria to chromosome 2p in 17 families, without evidence for locus heterogeneity. Other authors have independently identified missense mutations in SLC3A1 in cystinuria patients. In this report we describe four additional cystinuria-associated mutations in this gene: a frameshift, a deletion, a transversion inducing a critical amino acid change, and a nonsense mutation. The latter stop codon was found in all of eight Ashkenazi Jewish carrier chromosomes examined. This report brings the number of disease-associated mutations in this gene to 10. We also assess the frequency of these mutations in our 17 cystinuria families.     

Metabolic heterogeneity of isolated cortical and juxtamedullary glomeruli in adriamycin nephrotoxicity.

The anticancer drug adriamycin (ADR) is selectively toxic to glomerular cells when administered intravenously (5 mg/kg b.w.) to female MWF/Ztm rats. Recent data have shown that the proteinuria associated with the lesion does not occur in cortical glomeruli, suggesting the selective injury of juxtamedullary glomeruli. In the present study, the effect of ADR on glomerular metabolism was studied with special reference to possible differences between cortical and juxtamedullary glomeruli. On day 7 after ADR treatment, cortical and juxtamedullary glomeruli were separately isolated by the sieving method and 14C glucose oxidation to 14CO2 and the incorporation of 3H proline into macromolecules were measured in vitro and used to study target selective injury in ADR-treated rats compared to control rats. The investigations revealed differences in the response of cortical and juxtamedullary glomeruli to ADR. ADR treatment increased proline incorporation over a 4-hour incubation period in both glomerular populations compared to controls, but the effect was significantly (p less than 0.05) more pronounced in juxtamedullary glomeruli (juxtamedullary: 187 +/- 8% of control; cortical: 167 +/- 4% of control). Glucose oxidation was enhanced after 4 h only in juxtamedullary glomeruli (juxtamedullary: 132 +/- 3% of control; cortical: 82 +/- 10% of control). These data show that glomerular damage caused by ADR is associated with a stimulating effect on glomerular metabolism which is more marked in juxtamedullary than in cortical glomeruli, thus indicating a heterogenous response of different glomerular populations and supporting the concept that the selective damage of juxtamedullary glomeruli accounts for the proteinuria.     

The Synthesis and Biological activity of a Highly Selective Adenosine A2a. Receptor Agonist

Abstract

Three novel nucleosides 1, 2, and 3 were prepared that contained side chains at the 2-position of adenosine. Compound 1 was shown to be the most selective A_2a receptor agonist reported to date having an A₁/A₂ ratio of 2400. In addition, compound 1 was shown to reduce blood pressure in rats and dogs with only minimal effects on heart rate.