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R Bronson

Publications and source records attributed to R Bronson.

At least 73 records · Page 4Linked to original sources
PubMed1989

In vivo analysis of castanospermine, a candidate antiretroviral agent.

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine), an inhibitor of glycoprotein processing, has been shown to inhibit the human immunodeficiency virus type 1 (HIV-1) with acceptable toxicity in cultured cells. In contrast to reverse transcriptase inhibitors, castanospermine targets host enzymes. We have analyzed castanospermine in murine systems, using cultured cells as well as live animals. Plaque formation by Rauscher murine leukemia virus (RLV) was inhibited with a median inhibitory concentration (IC50) of 2 micrograms/ml. RLV-exposed BALB/c mice treated with a 20 day course of castanospermine starting 4 h postinoculation showed a dose-dependent inhibition of splenomegaly. Oral castanospermine therapy given to chronically RLV-infected mice prolonged median survival from 36 to 94 days when compared to untreated controls (p = 0.007). Castanospermine was better tolerated orally than intraperitoneally at the same dose. Toxic effects included weight loss, lethargy, and dose-dependent thrombocytopenia. At the highest intraperitoneal dose, lymphoid depletion occurred in thymus, spleen, and lymph nodes. We conclude that castanospermine is an active antiviral agent in animals and that prolonged oral administration is tolerable; however, when compared to 3'-azido-3'-deoxythymidine in the same murine system, castanospermine was less active and more toxic.

Alkaloids↗
PubMed1988

Murine chromosomal regions correlated with longevity.

In this longevity analysis of 360 BXD recombinant inbred female mice (20 different strains), 2 strains had very significantly shorter survival and 1 strain had very significantly longer survival than the other 17 strains; 4 other strains had less significant lengthening of survival compared to the other 13 strains in a proportional hazards model of survival. Mean survival on the shortest lived strain was 479 days; on the longest lived strain the mean survival was almost double (904 days). Ranges of survival within strain were very large (averaging 642 days), and strain accounted for only 29% of the variation in survival, showing that there are important environmental and/or special developmental effects on longevity even in this colony housed in a single room. Each strain had been typed for markers of 141 regions on 15 chromosomes; 101 of these markers had distinguishable distributions on the 20 strains. The two shortest lived strains had the same alleles for 63% of the markers. The single region most significantly correlated with survival (marked by P450, Coh, Xmmv-35 on chromosome 7) divided the mice into two groups with survival medians which differed by 153 days (755 days for mice with a B genotype; 602 days for mice with a D genotype). Evaluated individually, 44% of the genetic markers (including some markers on 11 of 15 chromosomes with any markers typed) were found to be significantly correlated with survival (P less than 0.05) although one would only expect 5% of the markers to be significant by chance. While studies of many markers should adjust for the multiple comparisons problem, one interpretation of these crude P values is that any experiment with only one of these "significant" markers typed would be likely to conclude that the marker was a significant predictor of survival. Two types of multiple regression models were used to examine the correlation with survival of groups of genes. When a proportional hazards model for survival was done in terms of genotype regions, a six genetic region model best correlated with survival: that marked by P450, Coh, Xmmv-35 on chromosome 7 (B allele lives longer), Ly-24 on chromosome 2 (B allele lives longer), beta 2M and H-3 on chromosome 2 (D allele lives longer) Lamb-2 on chromosome 1 (D allele lives longer), Ltw-4 on chromosome 1 (B allele lives longer), and the Igh area of chromosome 12 (Igh-Sa4, Igh-Sa2, Igh-Bgl, Igh-Nbp, Igh-Npid, Igh-Gte, Odc-8, and Ox-1; D allele lives longer).(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗
PubMed1988

Detection of antisperm antibodies on the surface of motile spermatozoa. Comparison of the immunobead binding technique (IBT) and the mixed antiglobulin reaction (MAR).

Investigators testing for antisperm antibodies have recently focused on tests that detect the Ig classes of the sperm-bound antibodies. The aim of this study was to compare the sensitivity of two of these tests, viz. the immunobead binding technique (IBT) and the mixed antiglobulin reaction (MAR). Twenty-one male or female sera were tested for IgG and IgA antisperm antibodies with the IBT and the MAR. The sera were selected on the basis of the IBT results, and the MAR was carried out without knowledge of these results. For IgG antisperm antibodies, there was a highly significant correlation between the two tests (P = 0.0043), whereas, for IgA antisperm antibodies, the correlation was poor (P = 0.2951), because the IBT revealed a positive reaction for IgA in sera in which no such antibodies could be detected by the MAR.

Autoantibodies↗
PubMed1988

Emigration from Israel 1950-1981: a simulation study.

"Using our mathematical model of a general theory of normative regulation, we have reproduced over 80% of the variance in the cumulative percentages of emigrants [from Israel], as well as the yearly percentages from 1950 to 1981. These results suggest that, except for a limited period following the 'Six-Day War' of 1967, no situation-specific explanations are needed to account for the trends in emigration from Israel, and the phenomenon can be adequately accounted for by the general theory of normative regulation in modern industrialized societies. Some practical conclusions to mitigate the process are drawn from these findings."

Asia↗
PubMed1987

Comparison of Bacteroides vulgatus strains in the enhancement of experimental ulcerative colitis.

Strains of Bacteroides vulgatus from a variety of sources were tested for their abilities to enhance the inflammatory response in an experimental model for ulcerative colitis. Although there were considerable differences noted in inflammatory responses when guinea pigs were immunized with the various strains, there did not appear to be any correlation between the source of the isolates and the severity of the carrageenan-induced lesions. Strains from patients with ulcerative colitis were no more active in the model system than were strains from patients with antibiotic-associated colitis or strains from a healthy human source. The antibody titer to the strain used for immunization did not correlate with the severity of the cecal ulcerations, as determined by histopathologic evaluation.

Animals↗
PubMed1985

Anti-sperm antibodies, detected by agglutination, immobilization, microcytotoxicity and immunobead-binding assays.

To determine the reliability of tests currently utilized in the detection of sperm-reactive antibodies, sera were provided as unknowns and studied without knowledge of the clinical histories. Four laboratories performed tray agglutination tests (TAT), three complement-dependent immobilization (SIT), and single laboratories sperm cytotoxicity (SCT), passive haemagglutination (PHA) and immunobead binding (IBB). Most investigators demonstrated an excellent correlation between duplicate sample results. Nearly all of the female sera were free of anti-sperm antibodies and positive results did not appear in greater frequency in women with unexplained infertility as compared with other categories. For the male sera, the highest incidence of anti-sperm antibodies in the infertile group (21% positive for sperm-reactive IgGs) was obtained by immunobead binding. The GAT and TAT results gave 7 and 12% positives, except for lower results in one laboratory. Sperm-reactive antibodies were detected most commonly in vasectomized men, with all assays except SCT and PHA. Of the newer techniques studied, IBB results correlated well with TAT, GAT and SIT, while SCT and PHA did not, suggesting that a different group of antibodies, perhaps directed against other sperm-associated antigens, was being detected by the latter procedures. In this light, emphasis was placed on the need to validate whether results of particular methodologies correlated with impaired sperm function and to develop methods that provided evidence for this premise, either on the basis of clinical criteria or altered gamete interaction in vitro.

Antibodies↗
PubMed1985

Conception rates in couples where autoimmunity to sperm is detected.

In men with autoimmunity to sperm, a varying proportion of spermatozoa in the ejaculate are found to have surface-bound immunoglobulins. We asked whether the extent of autoimmunity, as judged by this criterion, would have predictive value in determining the chance of conception. Infertile couples where husbands were found to have antisperm antibodies were treated for other factors leading to impaired reproduction, but no specific treatment was offered for reduction of these antibodies. The chance of pregnancy for those couples where autoimmunity to sperm was the sole definable factor leading to infertility was 15.3% when most spermatozoa were antibody-bound. A significantly greater number of wives whose husbands had less than 50% of their sperm bound by immunoglobulins conceived (66.7%; P less than 0.005).

Autoantibodies↗
PubMed1984

Traits that influence longevity in mice.

Analysis of genetic interactions in the segregating backcross [(C57BL/6 X DBA/2)F1 X DBA/2] mice revealed influences of genetic and environmental factors on life span. Using determinants of coat color (brown locus of chromosome 4 and dilute locus of chromosome 9), serologically determined H-2 antigens (chromosome 17) and sex as genetic markers, we studied the effects of these genes on longevity. The results suggested that genes in the brown locus (b) segment of chromosome 4, genes in a segment of the sex chromosomes and, to a more limited extent, genes in the segment of chromosome 17 which contains the H-2 haplotype all influenced longevity. The coat color (b locus) segment of chromosome 4 was associated with life span predominantly in females, whereas the chromosome 17 (H-2 haplotype) segment was associated with longer life primarily in males. The dilute locus d segment on chromosome 9 did not affect life span. Longevity appears to be influenced by interactions between genes in the chromosomal segment carrying H-2, those in the b segment, gender and the month of birth. Greater heterozygosity at the loci studied was associated with longer life span. Histopathological findings on mice that died at or after 28 months of age were comparable for all genetic combinations except that there was an increased frequency of lymphoma in females and an increased frequency of amyloidosis in males. Our analysis emphasizes the need for comprehensive studies of aging and longevity that would simultaneously determine the effects of several genetic regions and their interactions with the environment with respect to possible causes of death.

Animals↗
PubMed1981

Ability of antibody-bound human sperm to penetrate zona-free hamster ova in vitro.

Sera from men and women at risk for immunologic causes of infertility were screened for sperm-specific antibodies by a new test devised to assess directly the presence of immunoglobulins bound to the sperm plasma membrane. Passive antibody transfers to antibody-negative sperm of a fertile donor were performed with the use of sera that possessed iso- or auto-antibodies directed against the sperm head, including the acrosome and postacrosomal regions. The ability of these antibody-bound sperm to penetrate the zona-free hamster egg in vitro, a prerequisite for fertilization, was enhanced, as compared with the penetrating ability of antibody-free sperm of the same donor. These results indicate that the sperm-specific antibodies studied in these experiments, although bound to the sperm head, do not cause infertility by interfering with the acrosome reaction or gamete membrane fusion.

Animals↗
PubMed1981

The linearity of the volume/pressure response during intracranial pressure "reserve" testing.

The intracranial pressure "reserve" test seems to be the most reliable method of determining when the brain's natural mechanisms for pressure compensation for added intracranial volume have been compromised or exhausted. The test employs a timed sequence of intracranial fluid injections, but as a safety precaution injections are discontinued if intracranial pressure remains elevated more than 10 Torr over baseline. In this case, a linear extrapolation is then calculated to determine the elevation which might have been achieved by a full series of injections. However, this linear extrapolation has been criticised on the expectation that an exponential response should be expected. A series of experimental observations in dogs and baboons and a review of clinical records in humans have been made to determine the observed slope of increase following aliquot injection during performance of the intracranial pressure reserve test. In these species the observed response was actually linear in shape rather than exponential. This held true even for different initial baseline values and with different volumes of "lesion" balloon inflations in experimental animals. A theoretic explanation is proposed.

Animals↗
PubMed1979

Analysis of human spermatozoal fertilizing ability using zona-free ova.

An in vitro fertilization assay employing zona-free hamster eggs was used to analyze human spermatozoal fertilizing ability. Human spermatozoa were preincubated for 18 to 20 hours in Biggers, Whitten, and Whittingham's medium (1971) at a concentration of 1 X 10(7) sperm/ml prior to the addition of zona-free superovulated hamster eggs. Eggs were examined microscopically 2 hours later for evidence of swelling or decondensing sperm heads in the cytoplasm. A total of 6266 eggs were examined in assays for both suspected fertile and infertile donors; 50 eggs/sample were examined. The percentage fertilization was found to range from 14% to 100% in the suspected fertile group with an average of 56.3%. The sperm concentration in this fertile group ranged from 22 to 303 million/ml with an average of 114. The suspected infertile samples yielded fertilization rates of 10% or less and an average count of 50.6 million/ml. These data suggest that human spermatozoa fuse with the vitelline membrane of zona-free hamster eggs and decondense with varying efficiencies. The percentage of fertilization in this cross-species system did not show a significant correlation with sperm concentration or motility. However, suspected infertile samples always yielded 10% or less fertilization in this assay. This method may have potential value as a diagnostic tool in evaluating human spermatozoal fertilizing capacity which avoids the ethical and logistcal problems associated with fertilization of human eggs in vitro.

Animals↗