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Biomedical subjects

J L Riley

Publications and source records attributed to J L Riley.

At least 19 recordsLinked to original sources

Interferon (IFN) beta acts downstream of IFN-gamma-induced class II transactivator messenger RNA accumulation to block major histocompatibility complex class II gene expression and requires the 48-kD DNA-binding protein, ISGF3-gamma.

Interferon (IFN) gamma, a cardinal proinflammatory cytokine, induces expression of the gene products of the class II locus of the major histocompatibility complex (MHC), whereas IFN-alpha or -beta suppresses MHC class II expression. The mechanism of IFN-beta-mediated MHC class II inhibition has been unclear. Recently, a novel factor termed class II transactivator (CIITA) has been identified as essential for IFN-gamma-induced MHC class II transcription. We studied the status of IFN-gamma-induced CIITA messenger RNA (mRNA) accumulation and CIITA-driven transactivation in IFN-beta-treated cells and used cell lines that had defined defects in the type I IFN response pathway to address the roles of IFN signaling components in the inhibition of MHC class II induction. IFN-beta treatment did not suppress IFN-gamma-induced accumulation of CIITA mRNA. After cells were stably transfected with CIITA, endogenous MHC class II genes were constitutively expressed, and MHC class II promoters, delivered by transfection, were actively transcribed in CIITA-expressing cells. Expression of these promoters was significantly impaired by pretreatment with IFN-beta. These results suggest that IFN-beta acts downstream of CIITA mRNA accumulation, and acts in part by reducing the functional competence of CIITA for transactivating MHC class II promoters. IFN stimulated gene factor 3 (ISGF3) gamma was essential for IFN-beta to mediate inhibition of MHC class II induction, regardless of whether MHC class II transcription was stimulated by IFN-gamma or directly by CIITA expression. Results of these experiments suggest that inhibition of MHC class II in IFN-beta-treated cells requires expression of gene(s) directed by the ISGF3-IFN-stimulated response element pathway, and that these gene product(s) may act by blocking CIITA-driven transcription of MHC class II promoters.

DNA-Binding Proteins

Activation of class II MHC genes requires both the X box region and the class II transactivator (CIITA).

CIITA, a gene that can complement a transcriptional mutation of the major histocompatibility complex (MHC) class II genes, was tested for its ability to function as a coactivator, CIITA cDNA clones isolated showed alternative RNA splicing, but only one splice site combination was able to restore class II MHC gene expression. DNA-mediated transfection experiments showed that CIITA directs its activity through the X box element; the presence of CIITA leads to the formation of a higher order complex at the X box region; and CIITA contains a potent activation domain. These findings support the hypothesis that CIITA directly interacts with the MHC class II-specific transcription factors and is required for expression.

Alternative Splicing

Relationship between MMPI-2 cluster profiles and surgical outcome in low-back pain patients.

The purpose of this study was to investigate back surgery outcome differences based on Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profile types. Four homogenous subgroups were found from a hierarchical cluster analysis of 201 MMPI-2 profiles. These four clusters consisted of a Depressed-pathological profile, a conversion V profile (V-type), a neurotic Triad profile, and a within normal limit (WNL) profile. Patients in the WNL and Triad subgroups reported significantly more satisfaction with postsurgical improvement than did patients in the Depressed-pathological or V-type subgroups. The Triad subgroup also gave a more favorable subjective rating of surgical outcome than did patients in the Depressed-pathological or V-type subgroups. These groups also differed on measures of work status and nonwork-related physical activity levels but not on indices of pain.

Adult

Molecular analysis of G1B and G3A IFN gamma mutants reveals that defects in CIITA or RFX result in defective class II MHC and Ii gene induction.

Class II major histocompatibility complex (MHC) genes and the invariant (Ii) gene are inducible by interferon-gamma (IFN gamma) but not by interferon-alpha and interferon-beta. The promoter regions of these genes contain three regulatory elements that mediate constitutive and IFN gamma-induced expressions; however, none of the DNA-binding proteins that interact with these elements are regulated by IFN gamma. Recently, a gene coding for a transactivator (CIITA) of class II MHC genes that complements a HLA-DR-negative immunodeficiency has been isolated. Using one IFN gamma mutant cell line (G3A) that is selectively defective in HLA-DR and Ii induction, four lines of evidence are presented to show that CIITA mediates the IFN gamma induction of HLA-DR and Ii genes. Analysis of another mutant line, G1B, indicates that the lack of DRA and Ii gene induction by IFN gamma is correlated with the lack of RFX DNA binding activity, thus providing the link between RFX and an IFN gamma response.

Antigens, Differentiation, B-Lymphocyte

A radio telemetering capsule and demodulator for recording rumen motility.

A new pressure sensitive capsule for monitoring rumen activity has been developed. Surgery on the animal is not required for introducing the unit because it is small enough to be placed in the rumen using a stomach tube. The unit will transmit for several weeks and uses an inexpensive, commercially available pressure transducer as a sensor.

Animals

Experimental toxoplasmosis in calves and pregnant cows.

Experimental Toxoplasma gondii infections were studied in pregnant cows and in calves. In tests to compare their virulence, three strains of the toxoplasmal parasite were red to cats; then fecal oocysts were collected and given per os to calves. In tests to determine their effects, virulent tachyzoites or oocysts were given to 10 calves and to 22 pregnant cows by the oral, IV, or intraamniotic routes. Clinical signs were fever and inappetence. One cow in early gestation aborted 24 days after IV administration of tachyzoites. Gross and microscopic changes were slight and nonspecific. Toxoplasmas were isolaated from brain or liver of 4 cows, placenta of 2 cows, gastric contents of 2 near-term fetuses, and blood and tissues of calves. Toxoplasmas were not isolated from control cows.

Abortion, Veterinary

Body temperature changes in sows during the periparturient period.

Deep body temperatures were monitored with an implanted radiotelemetry device from 2 to 4 days prepartum to approximately 12 days postpartum in sows. The mean prepartum temperature of five normal sows was 38.6 degrees C, with a range of 38.3--38.9 degrees C. An increase in body temperature (1.4 degrees C) was associated with parturition. The increase in body temperature began about 12 hours before the first pig was born, peaked 1-2 hours after delivery of the last pig, and decreased during the first day postpartum but did not reach the prepartum values. Two days postpartum, the mean body temperature was about 1 degree C higher than it was during the prepartum period. The mean body temperature increased an average of 0.06 degrees C per day during the 12-day postpartum period. A diurnal pattern was evident in the body temperature variations.

Animals

A radiotelemetry transmitter for transmitting temperatures from small animals.

A small, reliable temperature-telemetry transmitter was designed and tested for use in small laboratory animals. It transmits a continuous signal that makes it very reliable. It can be constructed of standard small parts and contains and electric watch battery as a source of power. Two models were developed. One transmits at 100 MHz and its signal can be received on a standard FM tuner. The other model transmits at 40 MHz and provides a longer battery life.

Animals

Comparison of techniques for measuring the local and systemic responses to tuberculin in cattle.

Thermography of tuberculin skin reactions in cattle sensitized with Mycobacterium avium, Mycobacterium bovis, or Mycobacterium paratuberculosis was rapid and sensitive, but was not as specifically related to the homologous sensitization as was increased skin thickness at 48 and 72 hours. Systemic temperature responses were more completely monitored by radiotelemetry of intraperitoneally located temperature transmitters than by rectal thermometry, but the temperatures indicated by the 2 methods were nearly identical. The intraperitoneal transmitters showed that the systemic responses consisted of 1, 2, or 3 temperature peaks, and in 1 animal which had previously been exposed to a heterologous tuberculin, a hypothermic response developed. The systemic temperature responses were more specifically related to homologous sensitization than were dermal responses, but were more cumbersome to measure.

Animals

Effect of environmental temperature stress on intramammary infections of dairy cows and monitoring of body and intramammary temperatures by radiotelemetry.

Four dairy cows were stressed by exposure to hot and cold environments in tests to determine the effect of environment on milk yield, somatic cell counts, and California mastitis test scores of milk from all mammary quarters and on bacterial counts of milk from infected quarters. Two cows were held in temperature-controlled rooms for successive 5-day periods at moderate (21 to 28 C), cold (-16 C), moderate, hot (36 to 37 C), and moderate environments. The cold and hot sequences were reversed for the other 2 cows. Temperature transmitters were surgically implanted in the skeletal muscles of the loin and gluteal regions; however, only one of these transmitters (gluteal region) functioned continuously throughout the experiment. At the end of this experiment, a transmitter was implanted in the gland cistern of a rear quarter of 1 cow, and the sequence of holding in the cold before the hot environment was used. Mean body temperature was approximately 1 degree higher (39.2 C) in the hot room (1 cow) and 3 to 4 degrees lower (35 C and 33 C), respectively, for 2 cows) in the cold room than that during the moderate temperature periods. A similar comparison showed that the mean intramammary temperature was 1 to 2 degrees higher (39.5 C) in the hot room and approximately 9 degrees lower (29.4 C) in the cold room. Exposure of the cows to hot and cold environments caused a greater loss in milk production in the 2 medium-yielding cows (23 to 28 kg/day) than in the 2 low-yielding cows (9 to 13 kg/day). The effect of the extreme temperatures on the somatic cell counts in uninfected quarters was limited to only a few quarters and was inconsistent (mean counts increased and decreased at both temperatures). The California mastitis test reactions showed no consistent changes during periods of heat and cold stress. Also, the effect of the environmental temperature on the intramammary infections also was inconsistent. The effect on bacterial counts appeared to vary with the type of organism. Some mean counts decreased in the heat and cold (Streptococcus agalactiae, Micrococcus sp), some increased (Pseudomonas sp), and another seemed independent (Streptococcus uberis) of the environmental temperature at which the cow was held.

Animals

Upper respiratory infection of lactating sows with transmissible gastroenteritis virus following contact exposure to infected piglets.

Ten breeding sows were left in direct contact with their newborn piglets that had been experimentally infected with transmissible gastroenteritis (TGE) virus. All sows became infected with the virus. The sows developed fever and showed mild clinical signs of the disease for a few days. The sows excreted virus in the nasal secretion, feces, and milk during the acute febrile phase of illness. Virus was isolated from the nasal secretion of one sow as early as 20 hours after contact exposure to the infected piglets. At necropsy, the virus was more frequently isolated from the tissues of the upper respiratory tract than from small intestines; this finding indicated that the TGE coronavirus replicated in the upper respiratory tract and induced an acute respiratory infection in susceptible adult swine. Neutralizing antibody was present in the sera 8 sows after 12 to 36 days during the convalescent period. From these results, we conclude that susceptible sows in direct contact with ill piglets can become infected and by excreting virus can serve as a source of TGE virus for other susceptible pigs on the premises.

Administration, Oral