Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors.

Rat liver 6-phosphofructokinase (ATP-D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) was partially purified free of interfering enzymes by a rapid procedure. Fructose 2,6-bisphosphate, at micromolar concentrations, greatly stimulated the enzyme by increasing its affinity for fructose 6-phosphate and relieving the inhibition by ATP. Its action was synergistic with that of AMP. As a stimulator of liver phosphofructokinase, fructose 2,6-bisphosphate was approximately 1000- and 2500-fold more efficient than fructose 1,6-bisphosphate and glucose 1,6-bisphosphate, respectively. The concentration at which a half-maximal effect was obtained with the hexose bisphosphates was dependent upon the experimental conditions. It was relatively high at physiological concentrations of substrates, AMP, and Pi, and under these conditions the positive effect of fructose 1,6-bisphosphate was no longer detectable. This was probably due to the negative effect of fructose 1,6-bisphosphate as a reaction product inhibitor. It is concluded that fructose 2,6-bisphosphate rather than fructose 1,6-bisphosphate controls, in association with other effectors, the activity of phosphofructokinase in the liver.     

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.     

Blood rheological responses to running and cycling: a potential effect on the arterial hypoxemia of highly trained athletes?

To investigate 1) the blood rheological responses to high training volume and 2) the potential effect of these responses on arterial hypoxemia induced during submaximal running and cycling, 10 triathletes performed an incremental cycle test, 20 minutes of running (R), and 20 minutes of cycling (C). All trials were performed at nearly 75 % of VO2max. Hematocrit (H), blood viscosity (etab), plasma viscosity (etapl), index of erythrocyte rigidity (Tk), changes in plasma volume (DeltaPV), pulmonary diffusing capacity (DLco), and arteriolized blood gas (PaO2) were measured before and after each trial. Pulse oxymetry (SpO2) and cardioventilatory data were collected continuously. A significant increase in etab, etapl, and H was noted after R and C with respect to pre-exercise, whereas DeltaPV decreased, with a greater decrease after C. Tk was significantly higher after R than after C. A significantly greater drop in DLco was noted after C compared with R. SpO2 decreased significantly more during R, as did PaO2. We conclude that blood rheological responses are specific to running and cycling. Cycling induced a sharp decrease in plasma volume, which could partially explain the greater DLco alteration. Running was characterized by an increase in Tk, which could be implicated in the severity of the drop in arterial oxygenation observed.     

Field and laboratory testing in young elite soccer players

Aim: To determine if there are correlations between the physical fitness of young soccer players assessed by field and laboratory testing. METHODS: Thirty four male soccer players took part in the study (mean (SD) age 17.5 (1.1) years, height 177.8 (6.7) cm, weight 70.5 (6.4) kg). Maximal oxygen uptake (VO(2)MAX) during treadmill running and vertical jump height on a force platform were measured in the laboratory. Field tests consisted of a soccer specific endurance test (Bangsbo test) and 30 m sprint with 10 m lap times. RESULTS: The Bangsbo test correlated with the lowest velocity associated with VO(2)MAX (vVO(2)MAX; R(2) = 0.55, p<0.001), but not with VO(2)MAX. Sprint times at 30 m and 20 m were related to peak extension velocity and peak extension force measured during vertical jumping, but not to vertical jump height per se. The jumping force and velocity could explain 46% of the 30 m sprint performance (R(2) = 0.46, p<0.001). CONCLUSION: The Bangsbo test and 30 m sprint test correlate with vVO(2)MAX and vertical jump force and velocity respectively. The Bangsbo test does not give a good estimate of VO(2)MAX in young soccer players.     

Strong linkage disequilibrium between HLA-B*3913 and DRB1*0807 in Brazilians

The purpose of this research was to study the HLA-B39 distribution in 2560 healthy, unrelated, randomly selected individuals living in the southeastern region of Brazil (the states of Rio de Janeiro and S?o Paulo). Molecular methods were used to type HLA class I and II polymorphism: PCR-SSP, PCR-SSO, and PCR-SBT. HLA-B*39 was found in 7% (n = 182) of these individuals. HLA-B*3901, B*3906, and B*3913 were the most common alleles in this group (n = 57, 36, and 24, respectively). B*3913 was found associated with DRB1*0807 and DQB1*0402 in 16 of the 24 individuals and 13 of these were also associated with A*31012. This haplotype segregation was confirmed by family studies. Furthermore, in 5 of the 13 individuals carrying the A*31012, B*3913, DRB1*0807, and DQB1*0402 haplotype, HLA-DPB1*2701 was also present, suggesting that these alleles were found preferentially in cis association. DRB1-DPB1 linkage disequilibrium analysis was performed in 420 of the 2560 individuals and the association of DRB1*0807 with the uncommon DPB1*2701 was found to be highly significant (P <.0001). Because HLA-B*3913 and HLA-DRB1*0807 have been observed only in South American populations, it is possible that interlocus association has been selected to act on the same haplotype to collaborate in the class I and II restricted immune response to local pathogens and functional adaptation. Although numbers are small to predict which ethnic groups of the Brazilian population display this haplotype prevalently, it is possible to speculate that these data may have clinical application, such as in the selection of unrelated donors for bone marrow transplantation.     

'Honoring tradition, accepting new ways': development of a hepatitis B control intervention for Vietnamese immigrants

Background. Chronic hepatitis B infection rates among Vietnamese‐American adults range from 7 to 14%. Carriers of HBV are over 200 times more likely to develop liver cancer than non‐carriers, and Vietnamese males have the highest liver cancer incidence rate of any ethnic group in the USA (41.8 per 100,000). Culturally and linguistically appropriate interventions are necessary to increase hepatitis B knowledge, serologic testing, and vaccination rates among Vietnamese immigrants.

Methods. The authors engaged in qualitative data collection to inform the development of intervention materials including a video, pamphlet, and barrier‐specific counseling guidelines. Bilingual research assistants conducted 25 open‐ended qualitative interviews and six focus groups focusing on hepatitis B and liver cancer with a convenience sample of Vietnamese‐American men and women living in the Seattle area.

Results. Qualitative findings include beliefs about liver illness and health influenced by traditional Vietnamese and traditional Chinese medicine theory; beliefs about hepatitis B transmission and causes embedded in personal experiences and socio‐historical circumstances; and the value of health and a positive attitude. The video portrays a Vietnamese immigrant family struggling with the new knowledge that their healthy‐appearing son is a hepatitis B carrier. Print materials address knowledge resources and misconceptions about hepatitis B revealed in the qualitative data.

Discussion. Qualitative research provides valuable insight into unanticipated issues influencing health beliefs and behaviors relevant to specific populations and is essential to the development of effective health education materials, which necessarily draw upon local social and cultural contexts. The methods used in this study to develop culturally informed hepatitis B intervention materials for Vietnamese‐Americans translate well for the development of education outreach programs targeting Vietnamese and other immigrants elsewhere.     

Paediatric skin disorders encountered in an emergency hospital facility: a prospective study

To determine the frequency of skin disorders encountered in a paediatric emergency care unit and to evaluate the benefits of advice from a dermatologist, we prospectively recorded data of children admitted with skin disorders to the emergency care unit during a 5-month period. Diagnostic agreement between paediatricians and dermatologists evaluating the patients separately was assessed. Three hundred and ninety-five children (median age 3 years; interquartile 1-6) were included. Skin disorders represented 4% of all paediatric emergency care unit visits. Visits were considered as appropriate in 19-30% of cases according to different criteria. Six diseases accounted for 57% of cases: viral exanthema, urticaria, atopic dermatitis, varicella, diaper dermatitis and herpetic gingivostomatitis. The dermatologist modified the diagnosis in 42% of cases and the treatment in 30%. Greater emphasis on teaching the skin disorders encountered in this setting and efforts to provide easy access to advice from dermatologist would improve the quality of care.     

Pulmonary function during cycling and running in triathletes

AIM: Running performance has become key to the triathlete's overall performance. We still know relatively little about the factors that define the ability to perform a good run after cycling, however, and the perception of discomfort during the first minutes of this post-cycling running has yet to be satisfactorily explained. Pulmonary volumes (i.e., residual volume, RV, and functional residual capacity, FRC) have been demonstrated to be impaired after a cycle-run succession in triathletes but not after a run-run succession that is matched in terms of intensity and duration. Cycling in itself and/or the succession of two different exercises (i.e., cycling and running) may explain this phenomenon, but the exact mechanism has not yet been determined. METHODS: Thirteen young male triathletes participated in three different exercise trials: 30 min of cycling followed by 20 min of running (C-R), 30 min of control cycling (C) and 20 min of control running (R). Pulmonary volumes and flows were measured 10 min before and 10 min after each trial. During all trials, ventilatory data were collected every minute using an automated breath-by-breath system. RESULTS: The results showed that 1) C induced significant increases in RV, FRC and RV/TLC (2.31+/-0.18 vs 2.01+/-0.17 L, 4.35+/-0.24 vs 4.01+/-0.25 L, and 27.21+/-1.62 vs 23.98+/-1.55, respectively, after versus before C) and 2) there were no significant pulmonary volume or flow changes after C-R or R. CONCLUSION: We concluded that 1) cycling exercise in itself seems to increase the post-exercise pulmonary volume changes which could lead to respiratory muscle alterations and 2) one likely explanation for this finding appears to be the crouched position of cycling.     

A phase I trial of adenovector-mediated delivery of interleukin-2 (AdIL-2) in high-risk localized prostate cancer

Preclinical studies demonstrate that intratumoral delivery of adenovirus expressing IL-2 eradicates pre-established tumors in mice and confers immune protection from rechallenge. To explore the activity of AdCAIL-2 in prostate cancer, a Phase I clinical trial was conducted in patients with localized disease and Gleason score >7 or prostate-specific antigen (PSA) >10 plus Gleason score 7. A total of 12 patients were injected 4 weeks prior to prostatectomy in a dose-escalation study at doses of 10(9), 5 x 10(9) and 10(10) PFU of virus. No dose-limiting toxicity was observed. Side effects included perineal discomfort, hematuria, flu-like symptoms in two patients and urinary hesitancy in one patient. Pathology demonstrated an inflammatory response consisting predominantly of CD3+CD8+ T lymphocytes with areas of tumor necrosis. Intracellular cytokine staining of tumor-infiltrating lymphocytes demonstrated increases in both gamma-interferon and IL-4 secreting T cells after vaccination. PSA levels fell in five of five evaluable patients treated at the lowest dose (mean decline of 33.3%, range 17-69%). At higher doses, PSA values initially increased after injection, then fell to baseline prior to surgery. This trial demonstrates the feasibility and safety of intraprostatic adenovector-mediated IL-2 gene delivery.