Sublocalization of an Ataxia-Telangiectasia Gene Distal to D11S384 by Ancestral Haplotyping In Costa Rican Families

In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to ≈200 kb, between markers S384 and S535.     

Isolation of infectious pancreatic necrosis virus (serotype Ab) from diverse species of estuarine fish

Two significant fish kills occurred in the Pamlico River estuary (North Carolina, USA), one in December 1981 and January 1982, and the other in June 1982. The first involved only the southern flounder(Paralichthys lethostigma). Histopathologic examination of morbid and moribund flounder revealed extensive sloughing and necrosis of the mucosa of the pyloric caeca and intestine, and inflammation of the submucosa of the pyloric caeca. Brain and internal organ homogenates from morbid and moribund flounder were assayed on CHSE-214 cells, and a virus was isolated. Virus titers ranged from8.4 · 10² to 6.3 · 10⁷ TCID₅₀ per gram of tissue. Cross-plaque neutralization assays indicated that the southern flounder virus was infectious pancreatic necrosis virus serotype Ab. Immersion challenge showed the isolate is only slightly virulent for fry of brook trout(Salvelinus fontinalis). The second fish kill involved the southern flounder and six other species: hogchoker(Trinectes maculatus), Atlantic silverside(Menidia menidia), spot(Leiostomus xanthurus), Atlantic croaker(Micropogon undulatus), silver perch(Bairdiella chrysura), and striped mullet(Mugil cephalus). Virus was isolated from southern founder, hogchoker, Atlantic silverside, and spot. Neutralization assays indicated that the four isolates were nearly identical; however, the diversity of species affected suggests that the virus might not have been the specific cause of mortality.     

Cancer mortality among immigrant populations in Ontario, 1969 through 1973.

Ontario is home to a sizeable, recently established immigrant population whose cancer mortality has until now remained unexamined. The province''s six largest immigrant groups (British, Italian, German, Dutch, Polish and Soviet) were investigated to compare their cancer mortality experience with that prevailing in Ontario and in their countries of birth for the period 1969 through 1973. Standardized mortality ratios (SMRs) were computed from data from Statistics Canada and the World Health Organization (for 1971) for five sites of cancer. The rates of death from stomach cancer were significantly higher for the immigrant groups (except the Germans) than for the Canadian-born (SMRs 158.6 to 256.1) and were significantly lower for the immigrants (except the Dutch) than for the populations of their countries of birth (SMRs 26.5 to 72.9). The rates of death from colorectal cancer and cancer of the breast tended to be lower among the immigrants. Most male immigrants had high rates of death from lung cancer relative to the Canadian-born, whereas their female counterparts had relatively low rates. For most of the immigrant groups the rates of death from prostate cancer closely resembled those prevailing in the country of birth. Displacement of cancer mortality experience towards that in Ontario was most evident for Polish immigrants. It may have been too soon to see trends among the more recent immigrants (Italian, German and Dutch), who, for the most part, had not yet reached the age of highest cancer risk. Ontario should provide a valuable resource for further studies of lifestyle and environmental determinants of cancer.     

Inactivation of polioviruses and coxsackieviruses in surface water.

Inactivation rates of polioviruses 1 and 3 and coxsackieviruses A-13 and B-1 were determined in situ in the Rio Grande in southern New Mexico, using membrane dialysis chambers. Inactivation of the viruses was exponential, and the rates of inactivation were apparently affected principally by the water temperature. Stability of the viruses in river water differed, with poliovirus 1 and coxsackie B-1 being most stable. Typically 1-log reductions of infectivity at water temperatures ranging between 23 and 27 degrees C required 25 h for poliovirus 1, 19 h for poliovirus 3, and 7 h for coxsackie virus A-13. At water temperatures of 4 to 8 degrees C, the log reduction times for poliovirus 1 and coxsackievirus B-1 were 46 and 58 h, respectively. Results obtained with labeled poliovirus 1 and coxsackievirus B-1 and with infectious ribonucleic acid indicate that inactivation was due to damage to viral ribonucleic acid. Virus-inactivation rates were also affected by heat sterilization of river water, indicating the presence of a heat-labile or volatile inactivating factor. The inactivating factor in Rio Grande water was apparently present at a constant concentration over a 1-year period.     

Structural and compositional changes associated with chlorine inactivation of polioviruses.

Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation.     

T lymphocytes responding to Mls-locus antigens are Lyt-1+, 2− andI-A restricted

We have investigated primary and secondary responses of mouse splenic T cells to strong mixed lymphocyte stimulating antigens controlled by theMls locus using MHC-identical mixtures of cells. Our studies show that strong primaryMls-locus specific responses involve recognition of self I-A antigens, since BUdR and light suicide or F1 into parent radiation bone-marrow chimeras both demonstrate a preference of unprimed F1 T cells to respond to Mis-locus antigens associated with one parent's MHC antigens. Furthermore, conventional anti-I-A antisera and monoclonal anti-I-A antibody both inhibitMls-locus responses in an MHC-specific manner. Finally, as is typical of T cells responding to I-A antigens or to nominal antigens associated with self I-A,Mlslocus responses are mediated by Lyt-1⁺, 2^– cells. One striking finding in these studies was the very high frequency of cells capable of responding to Mls-locus antigens, the highest being 1/300 splenic T cells. This plus evidence for recruitment during primaryMls-locus responses may account for reports of a lack ofI-A restriction in secondary anti-Mls locus responses to strong Mls-locus antigens, a finding with which we concur. The possibility that these secondary responses between noncongenic strains of mice may be directed at other genetic loci is also discussed. These experiments leave open the question of the biological role of theMls-locus and of the very large number of T cells reactive to it.Abbreviations used in this paper MHC Major histocompatibility complex - MIg Mouse immunoglobulin - MLC Mixed lymphocyte culture - TCGF T-cell growth factor     

The binding of [3H]adenosine to synaptosomal and other preparations from the mammalian brain.

1. A high-affinity adenosine-binding site with Kd(adenosine) 0.5-1.3 microM was demonstrated in particulate and synaptosomal fractions isolated from the cerebral cortex of guinea pig, rat and ox. 2. Binding of [3H]adenosine to this site was inhibited by theophylline and by 2-chloroadenosine, but not by four other adenosine analogues. 3. Endogenous adenosine, found to be present in some preparations at approx. 1 pmol/mg of protein, diminished the binding capacity of the preparations for [3H]adenosine. 4. Addition of the adenosine deaminase inhibitor erythro-9-[1-(1-hydroxyethyl)heptyl]-adenine revealed the presence of a second lower affinity binding site with Kd (adenosine) 5-9 microM and a higher maximal adenosine-binding capacity. The inhibitor partially blocked binding to the high-affinity site in preparations from which adenosine deaminase had been removed by washing. 5. To preparations of particulate fractions maintained under iso-osmotic conditions, adenosine attachment was non-saturable and temperature-dependent, indicating the existence of an active uptake process. 6. The location and binding constant of the high-affinity adenosine-binding site suggest that it corresponds to the receptor site for adenosine-activated adenylate cyclase.