Conserved Gammaherpesvirus Protein Kinase Counters the Antiviral Effects of Myeloid Cell-Specific STAT1 Expression To Promote the Establishment of Splenic B Cell Latency.

Gammaherpesviruses establish lifelong infections and are associated with B cell lymphomas. Murine gammaherpesvirus 68 (MHV68) infects epithelial and myeloid cells during acute infection, with subsequent passage of the virus to B cells, where physiological B cell differentiation is usurped to ensure the establishment of a chronic latent reservoir. Interferons (IFNs) represent a major antiviral defense system that engages the transcriptional factor STAT1 to attenuate diverse acute and chronic viral infections, including those of gammaherpesviruses. Correspondingly, global deficiency of type I or type II IFN signaling profoundly increases the pathogenesis of acute and chronic gammaherpesvirus infection, compromises host survival, and impedes mechanistic understanding of cell type-specific role of IFN signaling. Here, we demonstrate that myeloid-specific STAT1 expression attenuates acute and persistent MHV68 replication in the lungs and suppresses viral reactivation from peritoneal cells, without any effect on the establishment of viral latent reservoir in splenic B cells. All gammaherpesviruses encode a conserved protein kinase that antagonizes type I IFN signaling in vitro. Here, we show that myeloid-specific STAT1 deficiency rescues the attenuated splenic latent reservoir of the kinase-null MHV68 mutant. However, despite having gained access to splenic B cells, the protein kinase-null MHV68 mutant fails to drive B cell differentiation. Thus, while myeloid-intrinsic STAT1 expression must be counteracted by the gammaherpesvirus protein kinase to facilitate viral passage to splenic B cells, expression of the viral protein kinase continues to be required to promote optimal B cell differentiation and viral reactivation, highlighting the multifunctional nature of this conserved viral protein during chronic infection. IMPORTANCE IFN signaling is a major antiviral system of the host that suppresses replication of diverse viruses, including acute and chronic gammaherpesvirus infection. STAT1 is a critical member and the primary antiviral effector of IFN signaling pathways. Given the significantly compromised antiviral status of global type I or type II IFN deficiency, unabated gammaherpesvirus replication and pathogenesis hinders understanding of cell type-specific antiviral effects. In this study, a mouse model of myeloid-specific STAT1 deficiency unveiled site-specific antiviral effects of STAT1 in the lungs and peritoneal cavity, but not the spleen, of chronically infected hosts. Interestingly, expression of a conserved gammaherpesvirus protein kinase was required to counteract the antiviral effects of myeloid-specific STAT1 expression to facilitate latent infection of splenic B cells, revealing a cell type-specific virus-host antagonism during the establishment of chronic gammaherpesvirus infection.

Non-Cardiac Chest Pain: management in the Ambulatory Clinic setting.

Non-cardiac chest pain (NCCP) is a common presenting complaint which can be better managed. This requires the recognition of clinical sub-groups with investigation and treatment tailored accordingly. The aim of this paper is to encourage more accurate diagnoses and the better recognition of the source of chest pain. We discuss the appropriate investigations and management of each clinical sub-group.

Fulminant pregnancy-related Churg-Strauss syndrome.

Pregnancy has not hitherto been known to influence the course of Churg-Strauss syndrome. We describe a case where relapse occurred in four successive pregnancies. The disease proved fatal in the last pregnancy when aggressive treatment failed to reverse fulminant cardiac disease.

Churg-Strauss syndrome.

The presentation of Churg-Strauss syndrome is most distinctive, permitting diagnosis on clinical grounds. It is a phasic disorder with allergic rhinitis and asthma initially, often followed by peripheral blood eosinophilia with eosinophilic tissue infiltrates. The vasculitic illness is the life-threatening phase, but it can be effectively suppressed by prompt treatment.

Effects of whole cottonseed or niacin or both on casein synthesis by lactating Holstein cows.

Forty Holstein cows in late lactation were offered diets containing niacin and whole cottonseed: 1) 0 g/d, 0%; 2) 0 g/d, 15%; 3) 6 g/d, 0%; and 4) 6 g/d, 15%, to evaluate effects on milk casein synthesis. Cows fed diet 1 had the highest DMI. The FCM (21.4 vs. 18.7 kg/d) and milk fat percentage (4.08 vs. 3.81) were higher for cows fed diet 1 than for those fed diet 4. Milk protein percentage (3.61 vs. 3.50) was higher for cows fed diet 1 than for those fed diet 2. Casein N, as a percentage of total N, was higher (71.9 vs. 68.0%) in milk from cows fed diet 1 than those fed diet 3. Insulin tended to be elevated in cows on the diets containing niacin, but glucose was not affected. Plasma niacin was elevated in cows on the diets supplemented with niacin compared with diet 1. Plasma AA were changed only slightly by treatments. The beneficial effect of niacin on milk casein synthesis, noted in our earlier work when cows were fed whole cottonseed, was not evident in this study with cows in late lactation and during hot weather.

Determinants of spermatogenesis recovery among workers exposed to 1,2-dibromo-3-chloropropane.

The purpose of this study was to investigate the determinants of spermatogenesis recovery among 30 azoospermic and 17 oligospermic workers who had a maximum of 18 months of exposure to 1,2-dibromo-3-chloropropane during 1976 to 1977. A maximum of 11 years of follow-up data were examined. Of the 26 azoospermic subjects who voluntarily participated in follow-up, 19 (73.0%) showed evidence of spermatogenesis recovery. Thirteen azoospermic subjects recovered to normospermic levels; however, their mean most recent sperm count (44.4 million/mL) was significantly lower (P less than .01) than the mean (88.8 million/mL) of the 17 oligospermic subjects who recovered to normospermic levels. The lack of spermatogenesis recovery was definitively shown to be job (drumming and canning) and, possibly, age related. Duration of exposure and the initial 1977 categorization of exposure (high, moderate, and low) were not predictive of recovery. Testicular atrophy was observed with azoospermia, and the testicles subsequently increased in size among those azoospermic subjects who returned to normospermic levels. The follicle-stimulating hormone level in 1977 was significantly associated with azoospermia as well as the likelihood of return to normospermia among the azoospermic subjects.

Responses of lactating Holstein cows to chilled drinking water in high ambient temperatures.

In Experiment 1, 12 lactating Holstein cows were provided drinking water of either 10.6 or 27.0 degrees C for 24 h/d in a changeover design to examine the effects of water temperature on feed intake, water intake, respiration rate, rectal temperature, plasma thyroid hormone concentration, and milk yield. The 1st wk of each 3-wk treatment period was for adjustment and the next 2 wk were comparison periods. Least squares means for DM intake as a percentage of body weight were 3.68 and 3.57 for 10.6 and 27.0 degrees C treatment groups. Water intakes in liters per kilogram of dry feed consumed as a percentage of body weight were 21.3 and 20.3. Respiration rates were 70.5 and 81.0 breaths per minute; rectal temperatures were 39.7 and 39.9 degrees C, Triiodothyronine averaged .88 and .75 ng/ml; thyroxine, 42.4 and 39.2 ng/ml; cortisol, 3.03 and 2.06 ng/ml; and progesterone in milk, 4.58 and 3.15 ng/ml for the 10.6 and 27.0 degrees C treatment groups. Milk yield averaged 25.9 and 24.7 kg/d and FCM averaged 25.6 and 23.6 kg/d, respectively. In Experiment 2, 24 cows given a choice of chilled or warm water showed a clear preference (about 98%) for the warm water. If cows are given chilled water of 10 degrees C continuously, no warm drinking water should be available. Chilled drinking water lowered respiration rates and body temperatures and increased feed intake and milk yield.

Monochloroacetic acid exposure: a case report.

Monochloroacetic acid exposure causes significant burns but can also be lethal following exposures of less than ten percent of body surface area. There have been two known survivors of significant monochloroacetic acid exposure. This is a case report of one of those survivors. The mechanism of toxicity is unknown, and attempts to relate monochloroacetic acid toxicity is to that of monofluoroacetic acid have yielded inconsistent results. The best mode of therapy is unclear, and no antidote has been proven effective, although ethanol and glycerol monoacetate have been suggested. The details of this case may be helpful to those faced with similar situations and to those investigating the toxicology of monochloroacetic acid.

Algoneurodystrophy following herpes zoster.

Algoneurodystrophy frequently follows an identifiable triggering event. It is not widely recognized that herpes zoster can precipitate algoneurodystrophy and three such cases are described here. In one, the affected dermatome did not correspond to the limb involved by the algoneurodystrophy.

Effects of whole cottonseed, niacin, and niacinamide on in vitro rumen fermentation and on lactating Holstein cows.

In Experiment 1, effects of whole cottonseed (0, 5, 15, or 30% of the total ration DM) on in vitro ruminal fermentation showed increased ruminal pH and ammonia concentration but lowered microbial protein. Acetic acid concentration was greatest with diets of 15 and 30% whole cottonseed, but propionate and total VFA concentrations were reduced by increasing whole cottonseed from 0 to 30%. In Experiment 2, neither niacin nor niacinamide (0, 100, 200, or 400 ppm) altered substantially fermenter pH or ammonia concentration. Both niacin and niacinamide increased synthesis of microbial protein. Acetate and propionate concentrations were not altered by treatment. Total VFA concentration tended to be lower as concentration of niacin and niacinamide increased. In Experiment 3, 28 Holstein cows were used to determine the effects of supplemental niacin on feed intake, milk yield, and composition. Cows were fed individually complete mixed diets ad libitum containing either: 1) 0; 2) .015; 3) .03; or 4) .06% niacin. There was a trend for lower milk fat test with niacin supplementation. Milk protein percentage was higher without niacin than with niacin at .015 or .03% in the diet, but daily milk and protein yields were higher with .06% versus .015% of niacin. Supplemental niacin did not affect casein nitrogen, lactose or minerals percentage, or concentrations of plasma glucose and insulin.

Chilled drinking water effects on lactating Holstein cows in summer.

In Experiment 1, 12 multiparous lactating cows (six per group) were offered drinking water ad libitum at temperatures of 10 or 30 degrees C in a switchback design. The treatment group received 10 degrees C water from 1235 to 2000 h and was then changed to 30 degrees C water for the remaining 16.5 h/d. The control group received 30 degrees C water 24 h/d. Respiratory rates, rectal temperatures, and rumen motilities were measured at 1100, 1440, and 1810 h, 3 d/wk. Water consumed was recorded for 1235 to 2000 h and 2001 to 1234 h of the next day. Water consumption for the treatment group was 3.90 L/h per cow compared to 5.40 L/h per cow for the control group from 1235 to 2000 h. However, the 10 degrees C water absorbed 65.6 kcal/h more heat than the 30 degrees C water. No differences were found in respiratory rates, rectal temperatures, rumen motilities, or milk yield. Cows that drank 10 degrees C water consumed 3.67 kg of feed DM/100 kg of body weight compared with 3.36 kg of feed for the controls. In Experiment 2, the same two groups of cows were offered 9.5 degrees C water ad libitum for 24 h/d or 27.5 degrees C water for a 48 h comparison. The treatment group tended to consume more water than the control group and to have lower respiratory rates and body temperatures.

Effects of niacin and whole cottonseed on ruminal fermentation, protein degradability, and nutrient digestibility.

Four mature nonlactating Holstein heifers fitted with ruminal and duodenal cannulae were used to investigate in vivo effects of niacin and whole cottonseed. Each heifer was assigned randomly to a treatment in a 2 X 2 factorial arrangement of treatment sequences within a 4 X 4 Latin square design. Heifers were fed isonitrogenous complete mixed rations individually twice daily. Diets contained corn-soybean meal concentrate, corn silage, chopped coastal bermudagrass hay, plus 1) 0% niacin and 0% whole cottonseed, 2) 0% niacin and 15% whole cottonseed, 3) .07% niacin and 0% whole cottonseed, or 4) .07% niacin and 15% whole cottonseed. Dry matter consumption, ruminal pH, ruminal ammonia and VFA concentrations, microbial N production, and DM and ADF digestion were not affected by treatment. Numbers of ruminal protozoa and RNA concentrations were reduced with whole cottonseed feeding and increased by addition of niacin. Whole cottonseed increased molar percentages of acetate while depressing propionate. Niacin supplementation resulted in greater digestion of both CP and NDF. Ether extract digestibility was highest in heifers fed whole cottonseed. Fiber digestion was not affected by whole cottonseed feeding.

A DNA polymorphism of an apoprotein gene associates with the hypertriglyceridaemia of primary gout.

Genomic hybridization analysis has been used to investigate allelic frequencies of the genes coding for the four major apoproteins of high density lipoprotein (HDL); apoproteins AI, AII, CII and CIII, in a group of Caucasian subjects with primary gout. An uncommon allelic variant of the apoprotein CIII gene (the S2 allele) was significantly more common among the patients with gout (9/48, 19%) than among normouricaemic controls who were either randomly selected (1/41, 2%, P = 0.03) or normotriglyceidaemic (0/33, 0%, P = 0.013). Approximately 46% (22/48) of the subjects with gout were hypertriglyceridaemic (with a serum triglyceride greater than 2.1 mmol/l). Of the 22 patients in this subgroup, 5 (23%) had the uncommon S1S2 genotype, which was also a significantly greater proportion than among the normotriglyceridaemic controls (P = 0.015). These data suggest that the hypertriglyceridaemia associated with primary gout may have a genetic basis. In contrast, we found no differences in the frequencies of restriction fragment length polymorphisms of the genes for apoproteins AI, AII and CII.

Decreased sensitivity to heparin in vitro in steroid-responsive nephrotic syndrome.

The in vitro heparin sensitivity of 18 nephrotic children was compared with that of 10 normal children and 13 children with other renal diseases. The influence of age on the heparin sensitivity of 52 normal subjects (aged 12 to 85 years) was also studied. The heparin sensitivity was calculated from the dose-response curve obtained when increasing amounts of heparin were added to plasma and the kaolin partial thromboplastin time (KPTT) was measured. There was a significantly-reduced heparin sensitivity in nephrotic children compared to the control children and a progressive decline in heparin sensitivity with age. In the nephrotic syndrome heparin-sensitivity correlated with albumin and triglyceride concentrations but not with antithrombin III, platelet factor 4, cholesterol, fibrinogen, heparin cofactor II or histidine-rich glycoprotein. Addition of exogenous albumin did not restore the heparin sensitivity of nephrotic plasma. Four patients with Type II hyperlipidemia had a normal sensitivity to heparin. The decreased sensitivity to heparin thus does not appear to be a consequence of the nephrotic state, and may be a reflection of an underlying disturbance of charged macromolecules in steroid-responsive nephrotic syndrome.