USE OF A PROGRAMMABLE CALCULATOR IN CARDIOPULMONARY PERFUSION

This study describes a hand-held, battery-powered, programmable instrument (Calculator Model SR-52) that can be taken directly into the operating room by cardiopulmonary perfusionists. Three programs are described in detail: 1) Cardiopulmonary perfusion parameters and estimated blood volume; 2) blood gas parameters and saturations, with temperature corrections; and 3) cardiopulmonary oxygen transfer and oxygenator efficiency. This inexpensive calculator allows perfusion personnel to manipulate easily-derived data into values which heretofore have required elaborate nomograms or special slide rules-or were not available within a reasonable computational time.     

Death on Denali: Fatalities Among Climbers in Mount McKinley National Park From 1903 to 1976—Analysis of Injuries,Illnesses and Rescues in 1976

Between 1903 and 1975 about 1 percent of climbers on Mount McKinley (Denali) and Mount Foraker in Alaska died. In 1976 a total of ten (1.7 percent) of 587 mountaineers died, but this rate of death was not significantly higher than previously.Nineteen percent of climbers in 1976 suffered major or minor injuries, illness or death. Acute mountain sickness (AMS), frostbite and fractures were common. Thirty-three rescues or retrievals of bodies were mounted at a cost of more than $82,000.Inexperience (particularly with arctic mountaineering), poor leadership, faulty equipment and undue reliance on rescue by helicopter contributed to the alarming incidence of accident, illness and death on big peaks in Mount McKinley National Park in 1976.     

Rotational flexibility of the human knee due to varus/valgus and axial moments in vivo

Knee ligamentous injuries persist in the sport of Alpine skiing. To better understand the load mechanisms which lead to injury, pure varus/valgus and pure axial moments were applied both singly and in combination to the right knees of six human test subjects. The corresponding relative knee rotations in three degrees of freedom were measured. Knee flexion angles for each test subject were 15 and 60 degrees for the individual moments and 60 degrees for the combination moments. For both knee flexion angles the hip flexion angle was 0 degrees. Leg muscles were quiescent and axial force was minimal during all tests. Tables of data include sample statistics for each of four flexibility parameters in each loading direction. Data were analyzed statistically to test for significant differences in flexibility parameters between the test conditions. In flexing the knee from 15 to 60 degrees, the resulting knee rotations under single moments depended upon flexion angle with varus, valgus, and internal rotations increasing significantly. Also, rotations were different depending on load direction; varus rotation was significantly different and greater than valgus rotation at both flexion angles. Also external rotation was significantly different and greater than internal at 15 degrees flexion, but not at 60 degrees flexion. Coupled rotations under single moments were also observed. Applying pure varus/valgus moments resulted in coupled external/internal rotations which were inconsistent and hence not significant. Applying pure axial moments resulted in consistent and hence significant varus/valgus rotations; an external axial moment induced varus rotation and an internal axial moment induced valgus rotation. For combination moments, varus/valgus rotations decreased significantly from those rotations at similar load levels in the single moment studies. Also, a varus moment significantly increased external rotation and a valgus moment significantly decreased internal rotation. These differences indicate significant interaction between corresponding load combinations. These results suggest that load interaction is a potentially important phenomenon in knee injury mechanics.     

Recombinant bovine neurokinin-2 receptor stably expressed in Chinese hamster ovary cells couples to multiple signal transduction pathways.

Neurokinins are a family of neuropeptides with widespread distribution mediating a broad spectrum of physiological actions through three distinct receptor subtypes: NK-1, NK-2, and NK-3. We investigated some of the second messenger and cellular processes under control by the recombinant bovine NK-2 receptor stably expressed in Chinese hamster ovary cells. In this system the NK-2 receptor displays its expected pharmacological characteristics, and the physiological agonist neurokinin A stimulates several cellular responses. These include 1) transient inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization, 2) increased out put of arachidonic acid and prostaglandin E2 (PGE2), 3) enhanced cyclic AMP (cAMP) generation, 4) increased de novo DNA synthesis, and 5) an induction of the "immediate early" genes c-fos and c-jun. Although NK-2 receptor-mediated IP3 formation involves activation of a pertussis toxin-insensitive G-protein, increased cAMP production is largely a secondary response and can be at least partially attributed to autocrine stimulation by endogenously generated eicosanoids, particularly PGE2. This is the first demonstration that a single recombinant neurokinin receptor subtype can regulate, either directly or indirectly, multiple signal transduction pathways and suggests several potential important mediators of neurokinin actions under physiological conditions.     

Androgen maintenance of erectile function in the rat penis.

Previous research has shown that the frequency and duration of penile erection is diminished after castration and that replacement with testosterone will restore the process. Using rats, the present study was designed to confirm that erection is androgen-dependent and to determine whether castration and androgen replacement affect the penile vascular smooth muscle responsiveness to vasoactive drugs. Blood pressure in the corpus cavernosum was measured directly during erections induced by electrical stimulation of the autonomic innervation of the penis. Maximal cavernosal pressure was markedly reduced after castration but was returned to normal levels if the castrated animals were treated with testosterone. Infusion of nitroglycerin (vasodilator) or phenylephrine (vasoconstrictor) resulted in a decline in cavernosal pressure in androgen-treated animals but not in castrated animals, even though the mean arterial blood pressure was strongly affected in all treatment groups by these drugs. When an inhibitor of nitric oxide synthesis was infused, cavernosal pressure was decreased in all groups, indicating that this substance is involved in penile erection. Taken together, these results show that androgens maintain the erectile process and may act specifically to support the responsiveness of the vascular smooth muscle to vasoactive drugs.     

Sensitivity of the vagina and uterus of mice neonatally exposed to estrogen or androgen to postnatal treatment with estrogen or androgen.

Newborn female BALB/cCrgl mice receiving 5 micrograms of testosterone or 0.01 micrograms of diethylstilbestrol daily for the first 5 days of life were examined at various times after secondary exposure to testosterone and 17 beta-estradiol, respectively. Neonatal administration of testosterone induced squamous stratification associated with constant cornification of the vaginal epithelium in intact mice. Later exposure to testosterone suppressed cornification, resulting in superficial epithelial mucification in almost all mice by 4 months of age. However, at 6 months of age, the incidence of mucification dropped to 58%. Cervicovaginal lesions developed in the groups of mice given neonatal testosterone in combination with later testosterone and sacrificed at 4 and 6 months of age. Continuous vaginal stratification was found in 14% of ovariectomized, neonatally diethylstilbestrol-treated mice at 13 months of age. The incidence of this ovary-independent change increased to 40% at 24 months of age. Postnatal estrogen replacement significantly increased the incidence of squamous stratification in these mice. Neonatal diethylstilbestrol treatment alone induced cervicovaginal lesions in 4.5% of ovariectomized mice at 13 months of age; secondary 17 beta-estradiol exposure significantly enhanced the development of lesions to 44%. However, at 24 months of age, there was no difference in the incidence of lesions in ovariectomized, neonatally treated mice with or without the secondary 17 beta-estradiol treatment. These results suggest that the effects of neonatal exposure to a relatively low dose of estrogen, androgen, or related substance may become obvious later in life as a result of later exposure to hormones.     

Whole-lake experimentation as a tool to assess ecosystem health,response to stress and recovery: the Experimental Lakes Area experience

The rationale and methods for and value of whole-lake experimentation are described using the Experimental Lakes Area (ELA), northwestern Ontario, as the example. The ELA consists of 46 lakes (< 100 ha in surface area), their watersheds, and several streams protected for research purposes in near-pristine boreal forest on the Precambrian Shield near Kenora, Ontario. Over more than 20 y, whole-lake experimentation has provided unique information on the effects on lakes of nutrient additions, acidification, Cd addition, and biomanipulation. Experiments are planned to study the effects of PCB addition and flooding. Recovery, mitigation, and remediation have been explored in some experiments. As well, the fate of radioactive metals in a lake and the effects of acidification on a poor fen and an upland watershed are studied. Comparison between the experimental systems and unmanipulated reference systems has proven to be essential. These reference systems also have a role in defining (absolute) aquatic ecosystem health for small, pristine Precambrian Shield lakes. The ELA experimental data base is available, as well, for calibrating indices of relative aquatic ecosystem health, i.e., environmental degradation, using the dose-responses of lakes to eutrophication, acidification, Cd addition, and other stressors.     

Progesterone maintenance of the placental progesterone receptor and placental growth in ovariectomized rats

These studies examine the trophic effects of progesterone (P) on the progesterone receptor (Rp) and growth of the decidua basalis (DB) and junctional zone (JZ) in the rat placenta. Pregnant rats were ovariectomized (Ovx) in mid-pregnancy and received steroid replacement therapy consisting of implantation of P pellets (25 mg) and injections of estradiol (E), 2 micrograms s.c., daily. Placental protein synthesis, measured by 3H-leucine incorporation in vitro, decreased more than 99% within 24 h of Ovx. However, treatment with P immediately after castration maintained control levels of synthesis. Delay of P treatment for 4 h caused a 60% decline in protein production measured 20 h later (p less than 0.01). Intraperitoneal implantation of a 50-mg pellet of the antiprogestin, RU-38486, in intact pregnant rats decreased protein synthesis by 50% within 6 h and by more than 90% 12 h and 24 h post-implantation (p less than 0.01). Growth of DB and JZ in Ovx rats treated for 48 h with P and/or E was studied both histologically and by changes in protein and DNA content. Rp binding activity was also measured by exchange assay under equilibrium conditions. Only P was able to reverse the effects of Ovx on growth of the DB and JZ. P also maintained Rp levels in the DB above those observed in Ovx and Ovx + E-treated groups (p less than 0.01). The Rp may be a constitutive product in the JZ since binding activity was not altered by Ovx or by steroid treatments. This study shows that P is clearly a trophic hormone of the maternal and chorioallantoic placenta and is essential for placental growth, cellular differentiation, and histological integrity.     

Interleukin 2-induced tyrosine phosphorylation. Interleukin 2 receptor beta is tyrosine phosphorylated

Interaction of interleukin 2 (IL2) with its high affinity membrane receptor complex (IL2R) is sufficient to induce proliferation of T lymphocytes. However, the biochemical mechanisms by which IL2 induces this process remain unresolved. The IL2R complex consists of at least two distinct polypeptides that bind IL2, a 75-kDa intermediate affinity subunit (IL2R beta) and a 55-kDa low affinity subunit (IL2R alpha). As indicated by Western blotting with anti-phosphotyrosine-specific antibodies and confirmed by phosphoamino acid analysis, we now demonstrate that interaction of the T cell growth factor interleukin 2 (IL2) with its high affinity receptor on IL2-sensitive human peripheral blood lymphoblasts induces tyrosine phosphorylation of proteins of 92, 80, 78, 70-75, and 57 kDa. IL2 induced tyrosine phosphorylation in YT 2C2 cells which express only the 75-kDa intermediate affinity IL2 binding molecule (IL2R beta) but not in cells which either express only the 55-kDa low affinity IL2 receptor molecule (IL2R alpha) or no IL2-binding sites. Therefore, IL2R beta, in the absence of IL2R alpha, appears sufficient to transduce the transmembrane signal leading to tyrosine phosphorylation. Two different antibodies reactive with phosphotyrosine specifically immunoprecipitated IL2R beta cross-linked to radiolabeled IL2. These findings suggest that IL2R beta is a substrate for the tyrosine kinase which is activated by IL2 binding to its receptor. Thus, like several other growth factor receptors, activation of the IL2R results in an increase in tyrosine phosphorylation with the receptor itself serving as one substrate.