Dietary fat and sex modify heterozygote effects of the rat fatty (fa) allele

Rats carrying one copy of the obesity gene fa may exhibit intermediate phenotypes between lean (+/+) and homozygous mutants (fa/fa). Previous data suggested to us that fa heterozygotes may be more sensitive than wild-type rats to high fat diets. To test this hypothesis, we generated +/+ and fa/+ rats and fed them diets containing 12% or 48% energy as fat for 7 wk. Energy efficiency was significantly greater in males than in females and in high fat-fed vs. low fat-fed rats. Perirenal fat pad weights were significantly greater in males than in females, in high fat-vs. low fat-fed rats and in fa/+ vs. +/+ rats. Adipose and soleus plasma membrane calcium-ATPase concentrations were significantly lower in rats fed the high fat diet. This protein was also lower in soleus of fa/+ rats compared with +/+ rats. There were significant diet x genotype interactions such that the high fat diet had the greatest effect on fat pads and calcium-ATPase in fa/+ rats. The results of the present study show heterozygote effects of the fa allele and suggest that these effects may be modulated by both sex-related factors and dietary manipulation.     

Polyubiquitin up-regulation in corpora lutea of prostaglandin-treated ewes

Genes that encode mRNAs for ubiquitin are activated by cells in metabolic distress. Cytosolic proteins that consequently become conjugated to ubiquitin are targeted for degradation. We hypothesized that ubiquitin mediates the endocrine demise of the corpus luteum induced by prostaglandin (PG) F2alpha. Indeed, polyubiquitin gene expression increased abruptly (within 2 h) in luteal tissues of ewes treated with PGF2alpha--before the precipitous decline in glandular progesterone accumulation indicative of functional luteolysis. A corresponding elevation in ubiquitin immunostaining was localized to large (PG-sensitive) luteal cells. It is suggested that luteal progesterone biosynthesis is disrupted by ubiquitination of steroidogenic regulatory proteins--perhaps those involved in the mechanics of mitochondrial delivery and side-chain cleavage of cholesterol.     

Sweep gas flowrate and CO2 exchange in artificial lungs

A simple analysis and graphic result are presented for characterizing the dependence of CO2 exchange on the sweep gas (ventilating gas) flowrate in artificial lungs. The analysis requires no knowledge of the device-specific mass transfer characteristics of an artificial lung, nor does it require detailed mathematical modeling or computer simulation. Rather, it uses appropriate normalization to establish generic features of the gas flow dependency of CO2 exchange that are applicable to all artificial lung devices. Principal results are that the transition from relatively gas flow-sensitive to gas flow-insensitive CO2 exchange occurs at sweep gas flowrates of approximately 40-60 times the CO2 exchange rate. Achieving a CO2 exchange rate within 85% of maximal (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate of no less than approximately 50 times the nominal CO2 exchange rate. When the sweep gas flowrate is less than 20 times the CO2 exchange rate, CO2 exchange is highly gas flow dependent and less than one-half the maximal possible rate.     

Bone mineral density in elite junior Olympic weightlifters

The purpose of this study was to examine the relationship of bone mineral density (BMD) to muscular strength in highly trained young male athletes in order to gain insights concerning the influence of heavy resistance training on BMD. Twenty-five elite junior weightlifters (age, 17.4 +/- 1.4 yr) and 11 age-matched controls (16.9 +/- 1.1 yr) volunteered for this investigation. Measurements of BMD (g.cm-2) utilizing dual energy x-ray absorptiometry were obtained for the lumbar spine (L2-4) and the proximal femur (neck; trochanter, Ward's triangle). The BMD values for the junior lifters were found to be significantly greater at all sites for the junior weightlifters compared with their age-matched control group. The BMD values of the spine and femoral neck of the junior weightlifters when compared with adult reference data (i.e., 20-39 yr old men) were found to be significantly greater. Both simple and multiple regression analyses demonstrated significant relationships of BMD with strength accounting for 30-65% of the variance. These data suggest that in elite junior weightlifters, muscle strength, highly specific to the sport of weightlifting, has a major influence on BMD due to the influence of the chronic overloads experienced in training.     

Very distal bypass for salvage of the severely ischemic extremity

Forty-six bypass grafts to tibial arteries distal to the ankle were performed in 35 patients for salvage of extremities threatened by gangrene or nonhealing ulcers (grade III, category 5) or ischemic rest pain (grade II, category 4). Most patients (80%) were diabetic, with severely calcified arteries, whom previously we would have considered as candidates for primary amputation. All reconstructions were performed with autologous saphenous vein. Inflow was from the common femoral artery in 5 (11%), the popliteal artery in 25 (54%), or the mid-tibial arteries in 16 (35%). Life-table analysis was used to calculate primary patency and limb salvage. Results were analyzed according to origin of inflow, outflow, or configuration of the conduit (in situ saphenous vein, n = 29 [63%], reversed saphenous vein, n = 11 [24%], or nonreversed saphenous vein, n = 6 [13%]). Overall cumulative primary graft patency at 2 years for all grafts was 72%, and the cumulative limb salvage rate was 89% for the same interval. No significant differences were seen in comparing grafts originating from the femoral or popliteal level with those arising from the tibial arteries. No significant differences were noted in graft patency or limb salvage among grafts with a posterior tibial, dorsalis pedis, or plantar artery outflow. No significant difference was noted between in situ saphenous vein grafts and reversed saphenous vein grafts. A significant decreased primary patency was noted for grafts performed with nonreversed, translocated saphenous vein. We conclude that bypass grafts to the ankle or foot vessels are beneficial and should be considered for limb salvage in extremities with gangrene, ischemic ulceration, or ischemic rest pain. In our experience, in situ saphenous vein grafts or reversed saphenous vein grafts performed similarly, whereas nonreversed saphenous vein grafts have a poorer prognosis. Vessel wall calcification requires a modification in technique for performance of these grafts but did not affect long-term performance or limb salvage, and thus should not be considered a contraindication to vascular reconstruction. The operative microscope was used in 61% (28 of 46) of these cases and found useful in creating these delicate anastomoses. Additional follow-up is needed to document the long-term results of these very distal reconstructions.     

Identification of PhoP-PhoQ activated genes within a duplicated region of the Salmonella typhimurium chromosome

The treatment of occlusive lesions in the innominate, subclavian, and axillary arteries has, until recently, been entirely surgical. Recently, advances in endovascular technologies have provided an alternative means of therapy. The advent of balloon angioplasty has resulted in some turmoil between medical specialties regarding patient selection and acceptable applications. Innovations in imaging, guidewire, catheter, stent, and balloon technology allow one to obtain percutaneous access and perform therapeutic procedures in a relatively safe manner. However, the excellent and time-tested results of surgery remain a standard for developing new procedures. Despite the appeal of less invasive techniques, the morbidity, mortality, and durability of novel treatments must equal or exceed those standards set by surgical procedures. Proponents of the endovascular options must familiarize themselves with advantages and disadvantages of surgical procedures. In a similar manner, surgeons have an obligation to understand the less invasive technologies as well. The clinician must uphold the best interests of the patient as a fundamental factor in the determination of a particular form of therapy. This paradox is well illustrated by consideration of occlusive lesions in the upper extremity.     

The role of the T lymphocytic cell cycle and an autogenous lymphocytic factor in clinical medicine

In this study 315 individuals (25 controls, 290 chemically sensitive immunocompromised patients) were investigated. Each patient had been on a standard therapy of avoidance of pollutants, nutritional supplementation, and injections of antigens for foods, and biological inhalants, but did not attain their immunological competence. Peripheral lymphocytes were collected and DNA histograms were constructed. The flow cytometer was used to evaluate the cell cycle, haematological, and other immunological profiles. From the other portion of the blood specimen, lymphocytes were propagated in vitro, harvested, and a lysate, termed the autogenous lymphocytic factor (ALF), was prepared. When treated with ALF, 88% of these individuals showed a significant (p < 0.001) clinical improvement which correlated with laboratory findings, involving regulation of abnormal cell cycles, increase in total lymphocytes and subsets T4, T8, (p < 0.05) and cell mediated immunity (CMI) response (p < 0.001). The ALF presumably acts as a biological response modifier. The cell cycle and ALF provide clinical tools for diagnosis and regulation of immunological incompetence.