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Spurious signals in DQF spectroscopy: two-shot stimulated echoes.

The most widely used technique for double-quantum filtered (DQF) single-voxel spectroscopy (SVS) is based on a symmetric PRESS sequence with two additional spatially unselective pi/2 pulses, one of which is usually frequency selective. The actual filtering, rejecting signals from all uncoupled resonances, can be done by suitable phase cycling of the rf pulses in successive shots, but in practice gradient filtering is always used. Under usual conditions the sequence repetition time is comparable to the spin-lattice relaxation time, and a stimulated echo is formed by five out of the ten rf pulses in two consecutive shots. This echo is not filtered out by the gradients, and additional phase cycling is needed to eliminate it. Its spatial origin is the full transverse slice selected by the last pulse of the PRESS sequence. The SVS shimming procedure may create an important field variation in this slice (outside the volume of interest VOI). Water singlet signals therefore appear in a band of frequencies other than 4.7 ppm, and remain unaffected by water suppression pulses. In practice phase-alternation schemes can reduce these spurious signals by several orders of magnitude, but even then they may mask the weak metabolite signals of interest. We describe a strategy to minimize these spurious signals and propose a 16-step phase cycling scheme that attenuates the stimulated echo in every two-step subcycle.

Algorithms↗

Sexual dimorphism and gonadal control of ultrasonic vocalizations in adult pine voles, Microtus pinetorum.

We investigated the vocalizations produced by adult pine voles during various social interactions by presenting an experimental animal with either an anesthetized or awake (unanesthetized) conspecific. Ultrasonic vocalizations (USVs) occurred frequently during tests in which an awake male was present, but were rarely detected in tests involving only awake females, or when a female was presented with an anesthetized conspecific. Higher rates of USVs were produced when males were tested with a familiar female than when tested with an unfamiliar male or female. Equivalent rates were produced when males were presented with either anesthetized or awake animals, but female-soiled bedding failed to elicit USVs from males. Sonic vocalizations (SVs) were produced by both sexes and were associated with aggressive behavior, but occurred only in tests between awake, unfamiliar animals. Castration greatly reduced and testosterone therapy restored USVs emitted by males in response to anesthetized conspecifics. Our results suggest that (i) USVs are emitted predominantly by males; (ii) familiarity enhances USV response; (iii) SVs are produced during aggressive interactions; and (iv) androgens regulate the production of USVs by males. Possible roles for pine vole vocalizations are discussed.

Animals↗

Phosphatidylcholine translocase: a physiological role for the mdr2 gene.

P-glycoproteins (P-gps) encoded by the mouse mdr2 and mdr3 genes were expressed in secretory vesicles (SVs) from the yeast mutant sec6-4, and their capacity to function as a lipid translocase/flippase was tested. An assay that uses a fluorescent phosphatidylcholine (PC) analog was developed to quantitate asymmetric lipid distribution in the outer and inner leaflets of the lipid bilayer of these vesicles. Mdr2 expression in SVs caused a time- and temperature-dependent enhancement of PC translocation to the inner leaflet of the membrane. The Mdr2-mediated effect was specific since expression of Mdr3 in these vesicles was without effect on the membrane distribution of PC. Increased Mdr2-mediated PC translocation was strictly ATP and Mg2+ dependent, was abrogated by the ATPase inhibitor vanadate and the P-gp modulator verapamil, but was insensitive to the presence of excess of the multidrug resistance drugs colchicine and vinblastine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of androgens on mRNA for a secretory protein of rat dorsolateral prostate and seminal vesicles.

The androgen dependence of a highly abundant mRNA found in the rat dorsolateral prostate and seminal vesicles has been investigated using a complementary DNA clone from a rat dorsal prostate library. The 1.5 kilobase (kb) mRNA codes for a 52 000 Da translation product which is processed to 49 000 Da in the presence of microsomal membranes. This product appears to correspond to the previously described SVS II protein secreted by rat seminal vesicles and can be immunoprecipitated with anti-SVS II antiserum. Dot hybridization assays indicated that the mRNA is abundant in the dorsal and lateral prostate glands and in seminal vesicles but not in the ventral prostate, coagulating gland or other non-accessory sex tissues. Castration of mature male rats reduces the 1.5 kb mRNA 10-fold in the seminal vesicles and 7-fold in the dorsolateral prostate in 9 days. Androgen administration to one-week castrates returned the mRNA level to normal in both tissues within 48 h. The levels of the 1.5 kb mRNA are very similar in the dorsolateral prostate and seminal vesicles at maturity but distinct patterns of developmental regulation of this gene exist in the two tissues. Between 3 and 6 weeks of age, the level of the 1.5 kb mRNA increases approximately 3-fold in the dorsolateral prostate while the increase in the seminal vesicles is more than 600-fold.

Age Factors↗

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction ≥0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗

Characterization of DIDS-sensitive ATP accumulation in brain synaptic vesicles.

ATP is an excitatory neurotransmitter in the central and peripheral nervous system. We investigated ATP accumulation in highly purified brain synaptic vesicles (SVs). Based on the amount of ATP accumulated in SVs under the conditions used, ATP is not transported against a concentration gradient but rather appears to have a Delta mu H(+)-independent mechanism. ATP transport was inhibited by DIDS and NEM, but was not affected by Mg(2+) or by pre-incubation with nucleotides. These results suggest a unique transport mechanism that does not involve exchange with other nucleotides or protons, unlike other known neurotransmitter transport systems.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The bleaching depth of a 35% hydrogen peroxide based in-office product: a study in vitro.

OBJECTIVES: The aim of the present study was to quantify the penetration of 35% hydrogen peroxide into enamel and dentine and to relate this to the resultant shade change of the tooth. METHOD: The crowns of 24 caries and developmental defect free human maxillary incisors were stained internally with a standardised tea solution. Twelve specimens were power bleached with light activated 35% hydrogen peroxide and 12 placed in water; both exposure times were 30min. Three different shade assessment methods (Vita shade guide [SG], shade vision system [SVS] and a chromometer) were employed prior to, after tea staining and after power bleaching/water treatments. Twelve specimens each from the bleach group and the water control water group were sectioned mesio-distally. An additional 12 specimens from the bleach and the control group were sectioned labio-palatally. The stain area for each specimen was measured using image analysis software. RESULTS: With tea staining, the mean changes in Vita shade guide units (SGU) ranged from 3.66 to 8.33. With the SVS system changes of 3.66-9 units were seen. Chromometer readings showed that following bleaching the L* values moved in the direction of black (3.8-6.7) and a* and b* values were in the red (0.3) and yellow (1.5) direction, respectively. Samples bleached and sectioned mesio-distally showed stain coverage of 28.6-39.4%, while palatal sections showed stain coverage of 58-72%. Control samples, whether sectioned mesio-distally or labio-palatally, showed staining throughout the dentine (97-100% coverage). CONCLUSION: A 35% hydrogen peroxide in-office bleaching gel demonstrated bleaching into dentine of uniform depth.

Analysis of Variance↗

Percutaneous angioplasty and stenting of the superficial femoral artery.

OBJECTIVES: The objectives of this study were to examine factors predictive of success or failure after percutaneous angioplasty (PTA) and stenting (S) of the superficial femoral artery (SFA) and to compare the results of PTA/S with a contemporary group of patients treated with femoropopliteal bypass. METHODS: A database of patients undergoing PTA and/or S of the SFA between 1986 and 2004 was maintained. Intention-to-treat analysis was performed. Patients underwent duplex scanning follow-up at 1, 3, and every 6 months after the intervention. Angiograms were reviewed in all cases to assess lesion characteristics and preprocedure and postprocedure runoff. Results were standardized to current TransAtlantic Inter-Society Consensus (TASC) and Society for Vascular Surgery (SVS) criteria. Kaplan-Meier survival analyses were performed to assess time-dependent outcomes. Cox proportional hazard analyses were performed to assess factors associated with patient survival and treatment efficacy. RESULTS: Three hundred eighty total limbs underwent PTA/S in 329 patients (67% male, 33% female; average age, 65 years). Mean follow-up was 1.8 years from the date of initial intervention. Indications for intervention were claudication in 66%, rest pain in 16%, and tissue loss in 18%. Runoff at the tibial level was 2.1 +/- 0.8 patent vessels. Mean SVS ischemia grade was 3.1 (range, 1 to 5). TASC lesion grades were A (48%), B (18%), C (22%), and D (12%). Angioplasty alone was used in 63% of cases. Primary treatment failure (inability to cross lesion) was seen in 7% of patients. There was one periprocedural death. Primary patency rates were 86% at 3 months, 80% at 6 months, 75% at 12 months, 66% at 24 months, 60% at 36 months, 58% at 48 months, and 52% at 60 months. Assisted primary patency rates were slightly higher ( P = not significant). By Cox proportional hazards analysis, patency of PTA/S was associated with higher preoperative ankle/brachial index ( P = .016) and the performance of angioplasty only ( P = .011). Failed or occluded PTA/S was associated with TASC C ( P < .0001) and TASC D lesions ( P < .0001). Patient death was associated with the presence of congestive heart failure ( P = .003). Subgroup analysis revealed that primary patency rates are highly dependent on lesion type (A > B > C > D, P < .0001). PTA/S patency for TASC A and B lesions compared favorably to prosthetic and venous femoropopliteal bypass. Surgical bypass was superior to PTA/S for TASC C and D lesions. CONCLUSIONS: PTA and stenting of the SFA can be performed safely with excellent procedural success rates. Improved patency of these interventions was seen with increased ankle/brachial index and the performance of angioplasty only. Worse patency was seen with TASC C and TASC D lesions. Patency rates were strongly dependent on lesion type, and the results of angioplasty and stenting compared favorably with surgical bypass for TASC A and B lesions.

Aged↗

Plaque excision with the Silverhawk catheter: early results in patients with claudication or critical limb ischemia.

OBJECTIVE: This study was conducted to detail the early experience after infrainguinal atherectomy using the Silverhawk plaque excision catheter for the treatment of symptomatic peripheral vascular disease. METHODS: A prospective database was established in August 2004 in which data for operations, outcomes, and follow-up were recorded for patients undergoing percutaneous plaque excision for peripheral arterial occlusive disease. Society for Vascular Surgery (SVS) ischemia scores and femoropopliteal TransAtlantic Inter-Society Consensus (TASC) criteria were assigned. A follow-up protocol included duplex ultrasound surveillance at 1, 3, and 6 months and then yearly thereafter. Standard statistical analyses were performed. RESULTS: During a 17-month period, 66 limbs of 60 patients (37 men [61.7%]) underwent 70 plaque excisions (four repeat procedures). Indications included tissue loss based on SVS ischemia at grades 5 and 6 (25/70), rest pain at grade 4 (22/70), and claudication at grades 2 to 3 (23/70). The mean lesion length was 8.8 +/- 0.7 cm. The technical success rate was 87.1% (61/70). Adjunctive treatment was required in 17 procedures (24.3%), consisting of 14 balloon angioplasties and three stents. Femoropopliteal TASC criteria included 5 TASC A lesions, 14 TASC B lesions, 32 TASC C lesions, and 19 TASC D lesions. Although 17 plaque excisions included a tibial vessel, no patient underwent isolated tibial atherectomy. The mean increase in ankle-brachial index was 0.27 +/- 0.04 and in toe pressure, 20.3 +/- 6.9 mm Hg. Mean duplex ultrasound follow-up was 5.2 months (range, 1 to 17 months). One-year primary, primary assisted, and secondary patency was 61.7%, 64.1%, and 76.4%, respectively. Restenosis or occlusion developed in 12 patients (16.7%) and was detected at a mean of 2.8 +/- 0.7 months. Restenosis or occlusion was significantly more common (P < .05) in patients with TASC C and D lesions compared with patients with TASC A and B lesions. Six (8.3%) of 12 patients underwent reintervention on the basis of duplex ultrasound surveillance results. Four (33.3%) of 12 patients experienced reocclusion during the same hospitalization, and amputation and open revascularization were required in two patients each. CONCLUSIONS: Percutaneous plaque excision is a viable treatment option for lower extremity revascularization. Outcomes are related to ischemia and lesion severity. Patency and limb salvage rates are equivalent to other endovascular modalities.

Catheterization, Peripheral↗

PACAP hybrid: a new PACAP receptor antagonist.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) hybrid, a synthetic antagonist, was investigated on NIH/3T3 cells containing PACAP receptor (R) splice variants (SVs). PACAPhybrid inhibited 125I-PACAP-27 binding to NIH/3T3 cells stably expressing PACAP-R basic, SV-1, SV-2 or SV-3 with an IC50 of 1000 nM. PACAPhybrid antagonized the ability of PACAP-27 to elevate cAMP regardless of the PACAP-R SV used. PACAP was more efficacious at increasing cytosolic Ca2+ in NIH/3T3 cells containing PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in cytosolic Ca2+ caused by PACAP-27 regardless of the PACAP-R SV used. PACAP was more potent at elevating c-fos mRNA using NIH/3T3 cells transfected with PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in c-fos mRNA caused by PACAP-27. These data suggest that PACAPhybrid is a useful PACAP receptor antagonist for PACAP-R SVs.

3T3 Cells↗

Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers.

The expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors in LNCaP, MDA-PCa-2b and PC-3 human prostate cancers grown in nude mice was investigated by RT-PCR. The expression of mRNA for GHRH was detected in LNCaP and PC-3, but not in MDA-PCa-2b prostatic carcinoma. RT-PCR analyses of mRNA isolated from LNCaP, MDA-PCa-2b and PC-3 cancers, revealed the presence of 720 and 566 bp products, corresponding to SV(1) and SV(2) isoforms of GHRH receptors. In PC-3 tumor membranes a radiolabeled GHRH antagonist [125I]-JV-1-42 was bound to one class of high-affinity binding sites (K(d)=1.81+/-0.47 nM) and maximum binding capacity of 332.7+/-27.8 fmol/mg membrane protein. The in vivo uptake of [125I]-JV-1-42 was observed in all xenografts of human prostate cancer, the tracer accumulation being the highest in PC-3 tumors. These results indicate that GHRH and SVs of its receptors, different from those found in the pituitary, are present in experimental human prostate cancers and may form a local mitogenic loop. The antiproliferative effects of GHRH antagonists on growth of prostate cancer could be exerted in part by an interference with this local GHRH system.

Alternative Splicing↗

Immunohistochemical characterization of clathrin assembly protein AP180 and synaptophysin in human brain.

Neurons rely on clathrin-mediated endocytosis for retrieving synaptic vesicles (SVs) at the presynaptic compartment after the release of neurotransmitters. The clathrin assembly protein AP180 is shown to be a regulator for this clathrin-dependent SV recycling pathway. AP180 is efficient in facilitating the formation of clathrin-coated vesicles and regulating their size, but its exact location in synapse is not clear. In this study, we compared the expression of AP180 with synaptophysin in the aged human brain using confocal immunofluorescence microscopy. Synaptophysin is well characterized for its association with SVs and therefore a commonly used presynaptic marker. We achieved satisfactory immunofluorescent labeling by using an autofluorescence blocker Sudan Black B and more photostable Alexa Fluor dyes. Although we found that AP180 had an overall expression similar to synaptophysin, the immunoreactivity for the two proteins did not always co-localize.

Aged↗

Development and evaluation of a method in vitro to study the effectiveness of tooth bleaching.

AIM: To develop and evaluate a reproducible intrinsic discolouration model in vitro, based on tea, which would allow the effectiveness of bleaching to be evaluated. METHOD: The crown portions of extracted human third molars were sectioned bucco-lingually in half. Colour assessments were made at baseline, post staining and post whitening using a standard clinical shade guide (SG), a shade vision clinical colorimeter system (SVS) and a reflectance chromometer. Internal staining employed a standard tea solution into which groups of five specimens were placed from 1 to 6 days. All assessments demonstrated maximum staining within one day. Groups of stained specimens were exposed to 1. Water (placebo control) 2. Enamel polished 3. Enamel polished and bleached through enamel 4. Bleached through enamel 5. Bleached through dentine 6. Bleached through enamel and dentine 7. Exposed to the bleach vehicle (minus active control). Control and bleach gel treatments were for 30 min. Comparisons of treatment effects were made using unpaired t-test on groups selected a priori for analysis. RESULTS: SG and SVS revealed that control and polish treatments had no or little effect respectively on tooth shade but all bleach treatments produced marked and statistically significant whitening effects and to a similar magnitude. Bleaching treatments returned the majority of specimens to the original shade or beyond representing a SG mean change of 13.8-15 shade guide units (SGU). Chromometer readings were consistent except that polishing alone increased tooth lightness slightly. CONCLUSIONS: Teeth were reproducibly stained internally, to provide a model in vitro by which to evaluate bleaching. The model, could be used to study many aspects of vital tooth bleaching, but has the limitation, without in vivo or in situ data, of cautiously extrapolating the effects in vitro to outcome clinically.

Colorimetry↗

A new algorithm for off-line automated emboli detection based on the pseudo-wigner power distribution and the dual gate TCD technique.

Research on microembolic signals (MES) using the dual-gate technique has shown promising results, when the time difference (Deltat) of a MES in two sample volumes (SVs) placed serially has been measured manually. On the other hand, the computerized discrimination of MES and artefacts has been reported not to be superior to algorithms based on a single SV. Therefore, a dataset containing MES as well as four types of artefacts was made to test a preliminary version of a new algorithm for automated emboli detection. We monitored 20 patients during carotid endarterectomy (n = 17) and heart surgery (n = 3). Two transcranial Doppler (TCD) signals with a partial overlap of the SVs were recorded online and analysed off-line with an algorithm based on three consecutive steps: 1. Is there an intensity increase in both channels (64-point FFT; 50% overlap)? 2. What is the expected time difference (Deltat), with the velocity measured in channel 1 as the calculation basis? 3. What is the 'exact' Deltat (pseudo-Wigner power function)? Two human experts decided whether a signal was a MES or belonged to one of the four artefact groups. Of a total of 97 MES, 28% (n = 27) could not be detected in the distal channel. Thus, 72% (n = 70) of the MES were present in both channels and could be analysed based on the abovementioned criteria. Of these 70 MES, 87% (n = 61) were correctly identified off-line. We assessed artefact rejection for four different types of artefacts: changes of TCD settings, probe movement, low flow artefacts and electrocautery. The reliability of artefact rejection was 98% for setting changes (n = 382), 96% for probe movement (n = 477) and 98% for low flow artefacts (n = 91), but only 68% for electrocautery (n = 264). These preliminary results are promising, but need careful interpretation: 28% of the MES were not detectable in the distal SV, probably due to a poor signal-to-noise ratio (SNR) and anatomical restrictions. Electrocautery signals were insufficiently rejected. However, even an artefact rejection of 96% can be insufficient if the number of MES is very small compared to the number of artefacts.

Algorithms↗

Has the changing nature of vascular surgery adversely affected scholarly activity.

OBJECTIVE: Because of reduced reimbursement and introduction of endovascular techniques into practice, vascular surgeons have increased clinical commitments. Therefore we hypothesized that the scholarly productivity of vascular surgeons has decreased. Study design An author-based Medline search was carried out for members of the Society for Vascular Surgery (SVS). The search included the period from 1985 to 1989 (era 1) for members in 1990, and from 1995 to 1999 (era 2) for members in 2000. Citations were assigned a type: basic science, clinical, case report, letter, or other; and a topic: cardiac, vascular, endovascular, transplantation, or miscellaneous. The main outcome measures were the proportion of members who published in each era and the rates of publication among authors. RESULTS: For era 1, 7069 citations were identified for 529 members, and for era 2, 6823 citations were identified for 615 members. Four hundred forty-two members were cited in era 1 (84%), compared with 443 (72%) in era 2 (P =.01). A significantly smaller proportion of members published clinical research, case reports, and other publications, but not basic science or letters. Excluding unpublished members, there was a median of 11 total publications per author in each era. There were significant reductions in the proportion of members publishing papers related to cardiac (from 36% to 21%), transplantation (8% to 4%), and miscellaneous (43% to 31%) topics, and a significant increase in papers related to endovascular topics (from 19% to 28%) from era 1 to era 2. Moreover, there was a significant increase in median number of vascular (from 5 to 8) and endovascular (1 to 2) papers per published member. Further, the proportion of vascular and endovascular citations compared with total citations increased from 44% to 56% in era 1 and from 3% to 10% in era 2. On a yearly basis, there was a steady decrease in the number of citations throughout era 2, whereas the number of citations in era 1 was relatively constant. CONCLUSIONS: Academic productivity was maintained for individual members who published across both eras, but a smaller proportion of the SVS membership published in era 2. There was also a progressive reduction in the number of publications during the 1990s.

General Surgery↗

Relations of Doppler stroke volume and its components to left ventricular stroke volume in normotensive and hypertensive American Indians: the Strong Heart Study.

Doppler echocardiographic measurement of time-velocity integral of blood flow across the aortic annulus ("stroke distance") or of stroke volume (SV) have been proposed as noninvasive measures of cardiac pump performance that could elucidate the hemodynamics of hypertension. To evaluate the performance of these measures of hemodynamic volume load in a population with a wide range of body build and other characteristics, we obtained technically adequate imaging and Doppler echocardiograms in 1,935 of 2,212 (87%) American Indian Strong Heart Study participants, without mitral regurgitation or segmental left ventricular (LV) dysfunction, in Arizona, Oklahoma, and South/North Dakota. The subjects ranged widely in age (48 to 81 years) and body mass index (17.0 to 62.6 kg/m2); 65% were women; 1,161 were normotensive and 774 were hypertensive. As a reference standard, LV and stroke volumes were calculated from LV internal dimensions by the Teichholz method. Doppler SVs were moderately related to LV SVs (r = 0.63), but Doppler SV was slightly lower in both normotensive (mean = 69.8 and 72.9 mL, respectively) and hypertensive subjects (71.1 v 73.6 mL). Aortic stroke distance was less closely related than was aortic annular area to LV SV (r = 0.34 v 0.40, P < .001). Aortic annular area (r = 0.44) but not stroke distance (r = 0.04) was moderately correlated with body surface area. Stroke distance was inversely related to annular area (r = -0.29) and in subjects stratified by aortic annular diameter 1.6 to 1.9, 2.0 to 2.1, and 2.3 to 2.9 cm, mean LV SV increased from 67 to 74 to 80 mL, but average stroke distance fell from 22.8 to 21.6 to 20.1 cm. Stroke distance also failed to identify gender differences in LV SV but did identify that due to obesity. Thus Doppler SV closely parallels independently measured LV SV but slightly underestimates SV in both normotensive and hypertensive adults, whereas aortic stroke distance yields misleading comparisons between genders or individuals of different body sizes.

Aged↗

Differential regulation of exocytosis by calcium and CAPS in semi-intact synaptosomes.

Using a novel approach to measure exocytosis in vitro from semi-intact synaptosomes, we establish that the Ca2+-dependent release of glutamate requires cytosolic factors for mobilization from the reserve pool. The cytosolic activity for glutamate release was not satisfied by CAPS, a soluble component required for norepinephrine (NE) release. Moreover, the CAPS-independent glutamate release from synaptic vesicles (SVs) was 200-fold less sensitive to Ca2+ than that required for dense core vesicles (DCVs). The differential regulation of exocytosis by CAPS, Ca2+, and potential novel cytosolic factor(s) suggests that the docking and fusion machinery controlling DCVs has diverged from that regulating glutamate-containing SVs.

Animals↗

Docking and fusion in neurosecretion.

A central issue in neurobiology concerns the mechanisms of membrane fusion that are essential for the rapid regulated delivery of neurotransmitters into the synapse. While many gene products are required for neurosecretion, recent research has focused on defining the core exocytotic machinery that is responsible for the docking of synaptic vesicles (SVs) and their fusion with the plasma membrane. N-ethylmaleimide-sensitive factor (NSF), soluble NSF attachment protein (SNAP) and SNAP receptor (SNARE) proteins are essential for fusion but may not be critical for SV docking. Current evidence suggests that NSF functions during an ATP-dependent step after docking but before fusion. NSF may function to liberate SNARE proteins from complexes so that the proteins on apposed membranes align in a parallel fashion to bring SVs into close contact with the plasma membrane for fusion.

Animals↗