Sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to the human immunodeficiency virus type 1 Vpu protein

CD4 is an integral membrane glycoprotein which functions as the human immunodeficiency virus receptor for infection of human host cells. We have recently demonstrated that Vpu, a human immunodeficiency virus type 1-encoded integral membrane phosphoprotein, induces rapid degradation of CD4 in the endoplasmic reticulum. Using an in vitro model system, we demonstrated that Vpu targets specific sequences in the cytoplasmic domain of CD4 to promote its degradation. In this report, we have further delineated regions within CD4 which are required for susceptibility to Vpu. Transfer of the CD4 cytoplasmic region into a heterologous protein, CD8, rendered the chimeric protein sensitive to Vpu-dependent degradation. In contrast, substitution of the CD8 transmembrane domain with the analogous region from CD4 did not confer sensitivity to Vpu. Finally, mutant forms of the CD4 protein containing the extracellular region alone or the extracellular and transmembrane regions linked to a heterologous cytoplasmic domain were not targeted by Vpu. Thus, sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to Vpu.     

Comparison of magnetic resonance volume flow rates, angiography, and carotid Dopplers. Preliminary results

BACKGROUND AND PURPOSE: We compared the results of conventional angiography, carotid Doppler, and magnetic resonance angiography volume flow rates to determine the clinical utility of volume flow rate assessment of blood flow to the anterior circulation in patients with carotid occlusive disease. METHODS: From 11 symptomatic patients, a total of 22 extracranial carotid arteries were studied with all three techniques. The studies were independently read, and regression analysis was used to compare the measurements. RESULTS: Carotid Doppler measurements of the distal extracranial carotid arteries were proportional to the inverse of the extracranial carotid volume flow rate (r = .53, R2 = 29%, P < .01), volume flow rates were proportional to the inverse of measured percent stenosis on angiography (r = .84, R2 = 71%, P < .01), and Dopplers were proportional to angiography (r = .94, R2 = 90%, P < .01). Symptomatic Doppler systolic velocity was significantly higher (P < .002), symptomatic measured stenosis was significantly higher (P < .002), and symptomatic volume flow rate was significantly lower (P < .01) than their respective asymptomatic-side values. These preliminary observations, however, may well change once a large data set, especially one in which more patients with high-grade carotid stenosis are included, is studied. CONCLUSIONS: Assessment of carotid volume flow rates by magnetic resonance angiography quantifies flow reduction secondary to atherosclerotic occlusive disease. The easily obtained flow data add both documentation of arterial flow characteristics related to internal carotid stenosis and information regarding the adequacy of collateral pathways.     

Detection and management of foreign bodies in soft tissue

The discovery and management of foreign bodies in soft tissue are challenging problems for emergency physicians. History, physical examination, and thorough wound exploration serve as the screening test for the presence of foreign bodies. Various radiographic studies can be performed to confirm the diagnosis, to identify the object's composition and shape, and to determine its approximate location in the tissues. Once the object is discovered, the clinician must weigh the potential harm of the foreign body in its current location against the risks of attempting removal.     

Femoral artery pseudoaneurysms: risk factors, prevalence, and treatment options

Femoral artery pseudoaneurysms (PSA or false aneurysm) develop in about 1% of patients undergoing procedures that require femoral artery cannulation. PSA prolong hospitalization, consuming health-care resources, and result in significant morbidity. We designed a study to review the prevalence, risk factors, and treatment of PSA. We performed a retrospective, case-controlled study of patients diagnosed with PSA at a large, urban, tertiary-care teaching hospital. We reviewed 48 patients with PSA for our study. The estimated prevalence of PSA was 0.28%, with identical rates found for procedures done in the interventional radiology department and in the cardiac catheterization suite. Logistic regression identified three independent risk factors for developing PSA: being female (odds ratio 2.62), having an intervention performed (odds ratio 3.22), and not having a closure device used (odds ratio 10.2). Patients with PSA had longer hospital length of stay than that of patients without PSA. We found no statistically significant difference in failure or complication rates for the four treatment options and that spontaneous resolution of PSA does not correlate with its size. Thrombin injection and observation are effective, low-complication treatment options.     

High affinity hormone binding to the extracellular N-terminal exodomain of the follicle-stimulating hormone receptor is critically modulated by exoloop 3

The human follicle-stimulating hormone receptor (FSH-R) consists of two distinct domains of >330 amino acids, the N-terminal extracellular exodomain and membrane-associated endodomain. The exodomain alone binds hormone with high affinity, whereas the endodomain is the site of receptor activation. Coordination of these two domains is essential for successful hormone action but little is known about their functional and structural relationship. In this communication, we report that exoloop 3 of FSH-R constrains follicle-stimulating hormone binding to the exodomain. When the FSH-R exodomain was prepared by truncating its endodomain, the hormone binding affinity of the exodomain was slightly improved, compared with the wild type receptor. The binding affinity was further improved by >3-fold when the exodomain was attached to the membrane-associated domain of CD8. These results suggest that the FSH-R endodomain attenuates hormone binding at the exodomain. As a first step to test this hypothesis, the 11 amino acids except Ala589 of exoloop 3 were individually substituted with Ala. Ala substitution for Leu583 or Ile584 improved the hormone binding affinity by 4-6-fold while totally abolishing cAMP induction, indicating an inverse relationship. The Ala substitution for Lys580 or Pro582 had a similar trend but to a lesser extent. This significant improvement in the binding affinity suggests that the four residues at the N-terminal region of exoloop 3 interact with the exodomain and constrain the hormone binding in the wild type receptor. This effect is specific since substitutions for other than the 4 residues did not improve the hormone binding affinity. Computer modeling shows that the 4 residues can be positioned on one side of exoloop 3. This result and the apparent inverse relationship of hormone binding and cAMP induction suggest that these two essential functions may work against each other. Therefore, hormone binding might be compromised to preserve cAMP inducibility while maintaining a reasonably high, but below maximum, binding affinity.     

Dependence of muscle VO2 on blood flow dynamics at onset of forearm exercise

The hypothesis that the rate of increase in muscle O2 uptake (VO2mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of approximately 2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase in VO2mus and blood flow was assessed from the mean response time (MRT), which is the time to achieve approximately 63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow and VO2mus both increased, with a MRT of approximately 30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 +/- 15.7 (SE)s] and VO2mus (50.2 +/- 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting valued in the above heart position (2.8 +/- 0.4 mmol/l) than in the below heart position (0.9 +/- mmol/l). At the lower power, both blood flow and VO2mus also increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2 transport.     

Professionally-led support groups for cancer patients: an intervention in search of a model

OBJECTIVE: The objective of this review was to evaluate the clinical and research literature on professionally-led support groups for cancer patients and to propose an approach that would address patients' needs from diagnosis through survivorship. METHOD: Computerized and manual searches, including Medline and Psychlit searches, were completed for reviews of the literature. Twelve research studies were identified that met our criteria for in-depth review. A clinical model emerged from discussions of an oncology study group based on theoretical formulations and clinical experience with oncology patients. RESULTS: We found that recent research suggests that professionally-led support groups are increasing in number and that participation in such groups seems to enhance patients' quality, and possibly even quantity, of survival. Despite this, little effort has been made to determine what type of group may be appropriate for which patients and when in their course of care. CONCLUSIONS: If psychosocial intervention, in the form of professionally-led support groups for cancer patients, is to be more effective, it should be guided by a model which takes into consideration the changing needs and concerns of patients over the course of illness and, in many cases, recovery. The authors present an outline delineating what such a model might entail.     

Central poststroke pain and Wallenberg''s lateral medullary infarction: frequency, character, and determinants in 63 patients

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.