Stable expression of mosaic coats of variant surface glycoproteins in Trypanosoma brucei

The paradigm of antigenic variation in parasites is the variant surface glycoprotein (VSG) of African trypanosomes. Only one VSG is expressed at any time, except for short periods during switching. The reasons for this pattern of expression and the consequences of expressing more than one VSG are unknown. Trypanosoma brucei was genetically manipulated to generate cell lines that expressed two VSGs simultaneously. These VSGs were produced in equal amounts and were homogeneously distributed on the trypanosome surface. The double-expressor cells had similar population doubling times and were as infective as wild-type cells. Thus, the simultaneous expression of two VSGs is not intrinsically harmful.     

Relations of total and abdominal adiposity to muscle sympathetic nerve activity in healthy older males

OBJECTIVES: We recently reported that skeletal muscle sympathetic nerve activity (MSNA) is related to total body and abdominal fatness in a pooled population of young and older males. Both MSNA and adiposity increase with age. Thus, it is not clear if the relation between MSNA and adiposity exists among older adults and if the age-related increase in MSNA is explained by increases in adiposity. We therefore tested the hypotheses that: 1) among older men, those with higher total body fatness and abdominal adiposity have higher MSNA and 2) MSNA is not different in healthy young and older men with similar total body and/or abdominal fatness. DESIGN: Older healthy men (63 +/- 1 y) were separated into higher and lower groups of body fat (26.9 +/- 0.8%, n = 9 vs 21.3 +/- 1.1, n = 10; P < 0.0001) and waist circumference (96.4 +/- 3.5 cm, n = 8 vs 86.2 +/- 1.5, n = 8; P < 0.01). Younger controls (26 +/- 1 y) were then matched with those in the older-lower groups for %body fat (21 +/- 1.1%, n = 10) or waist circumference (86.2 +/- 0.8 cm, n = 10). MEASUREMENTS: Total body fat was determined by hydrodensitometry, abdominal adiposity by waist circumference and resting MSNA by microneurography. RESULTS: Among the older subjects those in the higher %body fat and waist circumference groups had higher (P < 0.02) MSNA (47 +/- 3 and 48 +/- 4 bursts/min, respectively) than those in the lower groups (37 +/- 2 and 38 +/- 3 bursts/min). MSNA was directly related to %body fat (r = 0.52, P = 0.03) and waist circumference (r = 0.64, P = 0.007) in the older groups. MSNA was greater (P < 0.001) in the older-lower groups than in the young controls matched for %body fat (23 +/- 2 bursts/min) or waist circumference (24 +/- 3 bursts/min). CONCLUSIONS: 1) among healthy older men, higher levels of total body and/or abdominal adiposity are associated with higher levels of MSNA and 2) the age-related elevation in MSNA is reduced but not abolished when differences in adiposity are eliminated.     

Anesthesia type does not influence early graft patency or limb salvage rates of lower extremity arterial bypass

PURPOSE: The effect of anesthesia type on 30-day graft patency and limb salvage rates was evaluated in patients who underwent femoral to distal artery bypass. METHODS: Of 423 patients randomly assigned to receive general, spinal, or epidural anesthetic, 76 did not meet protocol standards and 32 had inadequate anesthesia. A chart review of the remaining 315 patients was undertaken to obtain surgical information not recorded in the original study. All patients were monitored with radial and pulmonary artery catheters. After surgery, patients were in a monitored setting for 48 to 72 hours and had graft function assessments hourly during the first 24 hours and then every 8 hours until discharge. RESULTS: Fifty-one patients were lost to follow-up (15 general, 22 spinal, 14 epidural). Baseline clinical characteristics were similar for the three groups except prior carotid artery surgery, which was more common in the spinal group. Indications for surgery were also similar except for a higher incidence of nonhealing ulcer in the epidural group. There were no differences among groups for 30-day graft patency with or without reoperation, 30-day graft occlusion, death, amputation, or length of hospital stay. CONCLUSION: These results suggest that the type of anesthetic given for femoral to distal artery bypass does not significantly affect 30-day occlusion rate, limb salvage rate, or hospital length of stay.     

Left ventricular hypertrophy, blood pressure and ACE genotype in untreated hypertension

It has been suggested that the deletion polymorphism of the angiotensin-converting enzyme (ACE) genotype may be important in the development of left ventricular hypertrophy (LVH). In order to test this hypothesis we investigated the interaction between blood pressure (BP), LVH and ACE genotype in 86 previously untreated hypertensive patients. Each underwent two-dimensional and Doppler echocardiography and ACE genotyping. There were no significant differences in BP, the parameters of left ventricular structure (including left ventricular mass index) or diastolic function between the three genotype groups. Additionally, there were no significant differences in the relationship between systolic BP and left ventricular mass index among the three genotype groups (II genotype, r = 0.46, P = 0.02; ID genotype, r = 0.42, P = 0.01; DD genotype, r = 0.34, P = 0.10; F = 0.38). In contrast to some previous studies, we have found in this group of previously untreated hypertensive subjects no evidence to suggest that the deletion polymorphism of the ACE genotype is important in the development of LVH.     

Hydrosalpingeal fluid inhibits in-vitro embryonic development in a murine model

Recent evidence describing a suboptimal clinical outcome in women with hydrosalpinges who undergo in-vitro fertilization (IVF) and embryo transfer suggests a potential deleterious effect of this fluid on in-utero embryo development. Consequently, we evaluated in-vitro mouse embryo development in the presence of hydrosalpingeal fluid (HF) collected from 10 infertile women of reproductive age. Chemical analyses showed both similarities and differences of these fluids to reported values for fluids collected from non-diseased Fallopian tubes. The HF had a significant deleterious effect upon mouse embryo cleavage and development to the expanded and hatched blastocyst stage, although the effect was variable among patients. Dilution of HF to 30% concentration with culture medium failed to negate this effect. This argues against the effect resulting from a relative lack of critical, supportive component(s) in the HF. Additionally, further experiments performed with cultures under an oil overlay significantly reduced the embryotoxicity of the HF. This evidence suggests there may be a lipophilic factor that can impair embryo development. The relatively poor IVF-embryo transfer success in women with proximally patent hydrosalpinges may be explained, at least in part, by reflux of a lipophilic embryotoxic factor(s) into the uterine cavity.     

Progressive muscular dystrophy in alpha-sarcoglycan-deficient mice

Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the alpha-sarcoglycan gene. To determine how alpha-sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed alpha-sarcoglycan- deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of alpha-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of alpha-dystroglycan association with membranes. In contrast, no change in the expression of epsilon-sarcoglycan (alpha-sarcoglycan homologue) was observed. Recombinant alpha-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan-sarcospan complex is requisite for stable association of alpha-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.     

Customized staple fixation in hand and wrist surgery

Fixation of small bones in the adult and the child's hands remains a challenge. The authors present a technique of bone fixation using customized staples made intraoperatively from K-wires (0.9-1.6 mm in diameter). Their specific purpose was to provide axial alignment and rotational stability for carpal bone fixation and for epiphysiodesis in phalanges. This technique was used in 14 cases (11 adult and three paediatric). No bone shattering, implant breakage, implant loosening or infection occurred. As K-wires are quite malleable, custom sized and shaped staples which follow the bone contours could be made to give a more exact fixation. All cases had satisfactory outcomes, achieving the preoperative objectives of bony fixation. This method is safe, precise and technically easy. It is also relatively cheap and only requires simple, standard instruments.