Functional analysis of myocardial performance in murine hearts overexpressing the human beta 2-adrenergic receptor

Transgenic mice overexpressing the human beta 2-adrenergic receptor gene were compared with wild mice type in terms of cardiac function, using a modified work-performing isolated murine heart preparation and on-line computer analysis. A preload-dependent experiment was performed, in which venous return was gradually increased in 5 mmHg increments from 5 mmHg to 25 mmHg. At each preload, aortic flow, left atrial pressure and aortic pressure were measured in all hearts, and from these parameters stroke volume, contractility, and cardiac index (cardiac output divided by body weight in g) were calculated and compared between groups. At increasing preload levels, the heart rates ranged from 322 beats/min (+/-29) to 369 beats/min (+/-39) in control mice and from 469 beats/min (+/-36) to 540 beats/min (+/-39) in transgenic mice. Cardiac index increased from 138 microliters/min/g (+/-13) and 48 microliters/min/g (+/-5) for transgenic and control mice, respectively at 5 mmHg preload to 262 microliters/min/g (+/-51) and 167 microliters/min/g (+/-15), respectively at 20 mmHg preload. The contractility in the transgenic mice were significantly increased at lower preload levels compared to control mice (1420 mmHg/s +/- 204 v 1187 mmHg/s +/- 127). An increase in myocardial adrenergic receptor density (100-200 fold) leads to significantly higher indices of cardiac function in transgenic mice compared to control mice. The increased heart rate leading to a positive inotropic effect in the hearts of transgenic mice is, at least in part, due to the overexpression of adrenergic receptors. These findings suggest a possible alternative method of establishing a positive chronotropic and inotropic state without the use of pharmacological agents.     

Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS

The neuropeptide Y Y2 receptor is one of six receptor subtypes mediating the multiform physiological actions of neuropeptide Y. The Y2 receptor has been demonstrated to be the most predominant receptor subtype in the human brain and appears to be involved in many neuropeptide Y actions, such as the regulation of locomotor activity, cardiovascular functions, memory processing, circadian rhythms and release of other neurotransmitters. We have recently demonstrated the widespread and abundant distribution of neuropeptide Y Y1 receptor messenger RNA in the human cerebral cortex (different laminar patterns within distinct cortical regions), hippocampal dentate gyrus and striatum. To assess a possible differential distribution of Y1 and Y2 receptor messenger RNAs, the regional expression of neuropeptide Y Y2 messenger RNA-containing cells in the human brain was analysed, in particular within the cerebral cortex and striatum. In situ hybridization experiments revealed the localization of the Y2 messenger RNA signal throughout all cortical regions, with the highest intensity per cell apparent in lamina IV, with the exception of the striate cortex, which showed an intense labelling primarily in layer VI. The striatum expressed low to undetectable levels of the Y2 receptor messenger RNA. The dentate gyrus and the CA2 region presented the highest hybridization signals, while a very weak Y2 messenger RNA expression was found in the CA1 region and subiculum. Positive Y2 messenger RNA hybridization signals were also detected in the lateral geniculate nucleus, amygdala, substantia nigra, hypothalamus, cerebellum and choroid plexus. These results demonstrate the widespread distribution of neuropeptide Y Y2 receptor messenger RNA in the human brain, with a pattern of expression distinct from the Y1 subtype, suggesting that these two receptor subtypes may mediate different neuropeptide Y functions in the human brain, mainly through actions on different neuronal systems.     

New pathway of heparan sulphate degradation. Iduronate sulphatase and N-sulphoglucosamine 6-sulphatase act on the polymer chain prior to depolymerisation by a N-sulpho-glucosaminidase and glycuronidases in the mollusc Tagelus gibbus

In current clinical practice, it is important to be able to evaluate the evidence supporting each of our actions. Physicians can no longer rely on tradition or habit; however, with the increasing number of journals available, it is impossible for the practicing clinician to keep abreast of all the relevant literature. One valuable method of gathering and summarizing the latest information and opinions is the use of round tables and consensus conferences. Published reports of round table and consensus conference findings can be invaluable in guiding the clinician.     

The influence of oxygen on the structure,fracture, and fatigue crack propagation behavior of Ti-8.6 Wt Pct Al

The effect of interstitial oxygen content on the structure, fracture, and fatigue crack propagation (FCP) behavior of Ti-8.6 wt pct Al was studied. Increasing oxygen was seen to raise the tensile flow strength of Ti-8.6A1 while coincidentally decreasing fracture ductility due to a transition in fracture mode from ductile rupture to cleavage or slipband fracture. The influence of oxygen onda/dn vs ΔK of Ti-8.6A1 in vacuum was found to vary with the R ratio. At R = 0.1, increasing oxygen led to slightly reduced FCP rates, while at R = 0.7, increasing oxygen from 500 to 1000 or 2000 ppm increased FCP rates. TheK _Ic of precipitation-aged Ti-8.6A1 was seen to be reduced with increasing oxygen. The detrimental influence of oxygen on fracture ductility andK _Ic is linked to oxygen’s influence on increasing slip planarity, particularly in the presence of α₂. The influence of deformation character (in particular, strain localization), rather than flow stress, in promoting cleavage-like fracture is discussed.     

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.     

Epidemiology and features of knee osteoarthritis in the Ivory Coast

We retrospectively studied 369 cases of knee osteoarthritis in 240 patients seen at the Cocody Teaching Hospital in Abidjan, Ivory Coast, from November 1984 through March 1989. There were 126 cases (34.14%) of patellofemoral osteoarthritis, 104 cases (28.18%) of femorotibial osteoarthritis and 139 cases (37.66%) of global knee osteoarthritis (defined as patellofemoral and femorotibial osteoarthritis in the same joint). There was a marked female bias (80.42% of patients). Onset was earlier in patellofemoral osteoarthritis (51.25 years) than in femorotibial osteoarthritis (57.85 years). Half the patients (51.25%) were housewives. The Akan and Mandé ethnic groups contributed 61.54% and 33.03% of patients, respectively. Obesity was present in 19.04% of cases of patellofemoral osteoarthritis and in 10.57% of cases of femorotibial osteoarthritis. Of the patients with femorotibial osteoarthritis, 20.20% had a history of arthritis of the knee and of those with global knee osteoarthritis, 12.23% reported a prior injury to the knee. Varus deformity was found in 24.03% and valgus deformity in 19.23% of the patients with femorotibial osteoarthritis.