Interaction of hyperthyroidism and hindlimb suspension on skeletal myosin heavy chain expression

We examined the novel interaction of hyperthyroidism and hindlimb suspension on the pattern of myosin heavy chain (MHC) expression (mRNA and protein) in skeletal muscles. Female Sprague-Dawley rats were assigned to four groups: 1) normal control (Con); 2) thyroid hormone treated [150 micrograms 3,5,3'-triiodothyronine (T3). kg-1. day-1] (T3); 3) hindlimb suspension (HS); or 4) T3-treated and HS (T3 + HS). Results show for the first time the novel observation that the combination T3 + HS induces a rapid and sustained, marked (80-90%) downregulation of type I MHC gene expression that is mirrored temporally by concomitant marked upregulation of type IIb MHC gene expression, as evidenced by the de novo synthesis of type IIb MHC protein in the soleus. The fast type IIx MHC isoform showed a differential response among the experimental groups, generally increasing with the separate and combined treatments in both the soleus and vastus intermedius muscles while decreasing in the plantaris muscles. The fast type IIa MHC was the least responsive to suspension of the MHCs and reflected its greatest responsiveness to T3 treatment while also undergoing differential adaptations in slow vs. fast muscle (increases vs. decreases, respectively). These results confirm previous findings that all four adult MHC genes are sensitive to T3 and suspension in a muscle-specific manner. In addition, we show that T3 + HS can interact synergistically to create novel adaptations in MHC expression that could not be observed when each factor was imposed separately.     

An important role for major histocompatibility complex class I-restricted T cells, and a limited role for gamma interferon, in protection of mice against lethal herpes simplex virus infection

Herpes simplex virus (HSV) inhibits major histocompatibility complex (MHC) class I expression in infected cells and does so much more efficiently in human cells than in murine cells. Given this difference, if MHC class I-restricted T cells do not play an important role in protection of mice from HSV, an important role for these cells in humans would be unlikely. However, the contribution of MHC class I-restricted T cells to the control of HSV infection in mice remains unclear. Further, the mechanisms by which these cells may act to control infection, particularly in the nervous system, are not well understood, though a role for gamma interferon (IFN-gamma) has been proposed. To address the roles of MHC class I and of IFN-gamma, C57BL/6 mice deficient in MHC class I expression (beta2 microglobulin knockout [beta2KO] mice), in IFN-gamma expression (IFN-gammaKO mice), or in both (IFN-gammaKO/beta2KO mice) were infected with HSV by footpad inoculation. beta2KO mice were markedly compromised in their ability to control infection, as indicated by increased lethality and higher concentrations of virus in the feet and spinal ganglia. In contrast, IFN-gamma appeared to play at most a limited role in viral clearance. The results suggest that MHC class I-restricted T cells play an important role in protection of mice against neuroinvasive HSV infection and do so largely by mechanisms other than the production of IFN-gamma.     

Synthesis and immunosuppressant activity of pyrazole carboxamides

A series of novel pyrazole carboxamides is disclosed that demonstrate strong immunosuppressant activity in rodent and human mixed leukocyte response (MLR) assays (IC50 < 1 microM). The synthesis, biological activity, mode of action, and pharmacokinetic properties of this new lead series are discussed.     

Influence of simulated altitude on the performance of five blood glucose meters

OBJECTIVE: To determine the reliability of five blood glucose meters (BGMs) at various simulated altitudes using a hypobaric chamber. RESEARCH DESIGN AND METHODS: Blood glucose levels (ranged from 1.5 to 26.3 mmol/l, according to the reference method) were measured in 18 venous blood samples by each BGM at 200, 1,000, and every 500 m up to 4,000 m in a hypobaric chamber, where temperature and humidity were held constant. RESULTS: Four BGMs underestimated and one overestimated blood glucose concentration while barometric pressure decreased. The average percent error varied in relation to simulated altitude from 0.26 +/- 4.8% (SD) at 200 m to -28.9 +/- 4.5% at 4,000 m (Glucometer 3; P < 0.05), from 28.4 +/- 5.7 to 49.3 +/- 5.9% (Accu-Chek Easy; P < 0.05), from -10.5 +/- 2.6 to 19.8 +/- 4.3% (Tracer, P < 0.05), from -5.5 +/- 2.6 to -11.2 +/- 3.0% (Reflolux; NS), and from 17.8 +/- 4.3 to 14.8 +/- 3.6% (One Touch; NS). The most accurate seemed to be the Reflolux, except for high blood glucose levels at simulated high altitudes. The One Touch II showed a good agreement, whatever the barometric pressure and the range of blood glucose concentrations. The highest underestimation was seen with the Glucometer 3. CONCLUSIONS: Except for the Accu-Chek Easy, low barometric pressure underestimated the BGM results in comparison with measurements taken at simulated low altitudes. The lack of accuracy and consistency of performance > 2,000 m should be known by diabetic patients practicing sports activities, such as trekking or skiing at high altitudes.     

Mechanism of platelet aggregation induced by a monoclonal antibody requiring Fc portion

A monoclonal antibody designated Apt4, which is IgG1, was produced by fusion of mouse myeloma cells to spleen cells from a BALB/c mouse immunized with normal human platelets. Apt4 whole IgG caused the aggregation of both platelet rich plasma (PRP) and washed platelets from normal subjects and a patient with Bernard Soulier syndrome but not those from two patients with the Type 1 Glanzmann's thrombasthenia. No aggregation was observed when Apt4 F(ab')2 fragments were used. Immunofluorescence study showed that both whole IgG and F(ab')2 fragments of Apt4 bound to fresh or formalin fixed platelets from normal subjects and a patient with Bernard Soulier syndrome but not to those from two patients with Glanzmann's thrombasthenia. Aggregation induced by Apt4 IgG was inhibited by EDTA (10 mM), PGE1 (1 mM), 2-deoxy-D-glucose/antimycin (1.4 uM), and apyrase (20 units/ml). Preincubation of normal PRP with monoclonal anti-GPIIb/IIIa or anti-GPIb antibodies completely or partially inhibited the Apt4-induced aggregation, whereas anti-GPIIIa antibodies have no effects on this activation. Monoclonal ant-Fc gamma RII antibody (IV.3) inhibited Apt4 induced aggregation. Immunoprecipitation of 125I-labeled platelet membrane lysate by Apt4 IgG showed two protein bands with a molecular weight of 145,000 and 95,000 daltons respectively under non-reducing condition, which are corresponding to GPIIb and GPIIIa. In conclusion, Apt4 antibody binds to GPIIb/IIIa complex and induces aggregation, requiring energy metabolism, calcium, ADP release and Fc portion of IgG to interact with Fc receptor, but independent of thromboxane A2 formation.     

Nutrient intake of elite sailors during a solitary long-distance offshore race

The purpose of the present study was to determine the nutritional intake of 11 skippers during the four stages of a solitary long-distance offshore race. Body weight significantly decreased during the race (-1.31 +/- 0.32 kg, range 3.5 to 0.1 kg, p <.01). Total daily energy intake was 18.53 +/- 0.71 MJ x day-1 during the race, and it correlated negatively with the rate duration of each leg. Energy intake during the race was 19% greater than that determined for a subgroup of 5 sailors during a control period 2 months after the race. Nutrient intake expressed as percentage calories of total energy was estimated at 50%, 35%, and 15% for carbohydrate, fat, and protein, respectively. Voluntary fluid intake decreased with increasing race duration (p<.001). Despite high energy intakes, sailors lost body weight during the solitary offshore race. It was not possible to conclude that this change in body weight was related to fluid loss and/or a discrepancy between energy intake and energy expenditure.     

HATP chemotherapy combined with Chinese traditional medications in treating acute promyelocytic leukemia

18 patients with acute promyelocytic leukemia (APL) were treated with HATP (Harringtonine, Adriamycin, Thioguanine, Prednisone) chemotherapy combined with chinese traditional medications. These medications are known to strengthen vital energy, promote blood circulation, remove stasis and clear toxic materials. 16 patients had complete remission (88.8%) and one partial remission with a total effective rate of 94.4%. Complete remission (CR) was achieved after 3 to 4 courses of treatment in most of the cases. 14 patients were still in CR at the completion of this study and the average duration of survival was 40.5 months. With the various therapeutic actions mentioned above, the traditional medications might decrease the toxicity of chemotherapy, reduce its side effects and prevent the occurrence of DIC. The combined use of traditional medications with chemotherapy may increase the rate and duration of CR as well as prolong the survival.