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PubMed2002

Relevance and practicability of internal mammary sentinel node biopsy for breast cancer.

OBJECTIVES AND METHOD: Recent observations in breast cancer patients undergoing sentinel lymph node (SLN) mapping, in which drainage can be traced to the internal mammary node (IMN) chain, have renewed interest in the staging and treatment of the disease. This paper discusses the relevance of internal mammary SLN biopsy and suggests an optimal procedure for the identification of the SLN in the IMN chain. RESULTS: Axillary lymph node (AX) and IMN status have similar predictive relevance for survival, while the involvement of IMNs has prognostic value for AX-negative as well as AX-positive patients. Although parasternal recurrence is fortunately rare after modified radical mastectomy or breast conserving surgery, if left untreated it not infrequently develops as clinically evident disease in patients with histologic involvement of IMNs. "Hot" internal mammary SLNs can be identified by means of lymphoscintigraphy and gamma-detection probe after peritumoral injection of radioisotopes. A positive internal mammary SLN biopsy would be an indication for internal mammary radiotherapy as well as adjuvant systemic treatment. However, the reported incidence of positive internal mammary SLNs is still lower than expected because the spread of radioactivity does not necessarily coincide with nodal involvement. CONCLUSION: Internal mammary SLN biopsy has proven to be relevant but not yet fully practical because more data are needed on the collection of a "Hot" internal mammary SLN and on pathologic involvement. This means that internal mammary SLN biopsy should be regarded as still investigative.

Breast Neoplasms↗
PubMed2003

Physiological coxa varus-genu valgus influences internal knee and ankle joint moments in females during crossover cutting.

This study evaluated the ankle and knee electromyographic, kinematic, and kinetic differences of 20 nonimpaired females with either neutral (group 1) or coxa varus-genu valgus (group 2) alignment during crossover cutting stance phase. Two-way mixed model ANOVA (group, session) assessed mean differences ( p<0.05) and correlation analysis further delineated relationships. During impact absorption, group 2 displayed earlier peak horizontal braking (anterior-posterior) ground reaction force timing, decreased and earlier peak internal knee extension moments (eccentric function), and earlier peak internal ankle dorsiflexion moment timing (eccentric function). During the pivot phase, group 2 displayed later and eccentrically-biased peak ankle plantar flexion moments, increased peak internal knee flexion moments (eccentric function), and later peak knee internal rotation timing. Correlation analysis revealed that during impact absorption, subjects with coxa varus-genu valgus alignment (group 2) displayed a stronger relationship between knee internal rotation velocity and peak internal ankle dorsiflexion moment onset timing ( r= -0.64 vs r = -0.26) and between peak horizontal braking ground reaction forces and peak internal ankle dorsiflexion moment onset timing ( r= 0.61 vs r= 0.24). During the pivot phase these subjects displayed a stronger relationship between peak horizontal braking ground reaction forces and peak internal ankle plantar flexion moment onset timing ( r= -0.63 vs r= -0.09) and between peak horizontal braking forces and peak internal ankle plantar flexion moments ( r= -0.72 vs r= -0.26). Group differences suggest that subjects with coxa varus-genu valgus frontal-plane alignment have an increased dependence on both ankle dorsiflexor and plantar flexor muscle group function during crossover cutting. Greater dependence on ankle muscle group function during the performance of a task that requires considerable 3D dynamic knee joint control suggests a greater need for frontal and transverse plane weight bearing tasks that facilitate eccentric ankle muscle group function to optimize injury prevention conditioning and post-surgical rehabilitation programs.

Adolescent↗
PubMed2005

Internal forces during object manipulation.

Internal force is a set of contact forces that does not disturb object equilibrium. The elements of the internal force vector cancel each other and, hence, do not contribute to the resultant (manipulation) force acting on the object. The mathematical independence of the internal and manipulation forces allows for their independent (decoupled) control realized in robotic manipulators. To examine whether in humans internal force is coupled with the manipulation force and what grasping strategy the performers utilize, the subjects (n=6) were instructed to make cyclic arm movements with a customized handle. Six combinations of handle orientation and movement direction were tested. These involved: parallel manipulations (1) VV task (vertical orientation and vertical movement) and (2) HH task (horizontal orientation and horizontal movement); orthogonal manipulations (3) VH task (vertical orientation and horizontal movement) and (4) HV task (horizontal orientation and vertical movement); and diagonal manipulations (5) DV task (diagonal orientation and vertical movement) and (6) DH task (diagonal orientation and horizontal movement). Handle weight (from 3.8 to 13.8 N), and movement frequency (from 1 to 3 Hz) were systematically changed. The analysis was performed at the thumb-virtual finger level (VF, an imaginary finger that produces a wrench equal to the sum of wrenches produced by all the fingers). At this level, the forces of interest could be reduced to the internal force and internal moment. During the parallel manipulations, the internal (grip) force was coupled with the manipulation force (producing object acceleration) and the thumb-VF forces increased or decreased in phase: the thumb and VF worked in synchrony to grasp the object more strongly or more weakly. During the orthogonal manipulations, the thumb-VF forces changed out of phase: the plots of the internal force vs. object acceleration resembled an inverted letter V. The HV task was the only task where the relative phase (coupling) between the normal forces of the thumb and VF depended on oscillation frequency. During the diagonal manipulations, the coupling was different in the DV and DH tasks. A novel observation of substantial internal moments is described: the moments produced by the normal finger forces were counterbalanced by the moments produced by the tangential forces such that the resultant moments were close to zero. Implications of the findings for the notion of grasping synergies are discussed.

Adult↗
PubMed2004

Comparison of rational pharmacotherapy decision-making competence of general practitioners with intern doctors.

OBJECTIVE: The aim of this study was to compare rational pharmacotherapy decision-making competency of interns (final-year medical students) who had received rational pharmacotherapy education (RPE), with their classmates at another medical school and general practitioners (GPs) who had not been exposed to RPE. DESIGN: A written, objective, structured clinical examination (OSCE), consisting of open and structured questions, was given to all participants. The participants were expected to make a treatment plan and prescribe for simple, uncomplicated beta-hemolytic streptococcal tonsillitis and mild-to-moderate essential hypertension patients, explain their proposed treatment plans and reasons affecting their drug choice. After the OSCE, a questionnaire to assess knowledge of the rational use of drugs was given to the participants. RESULTS: Fifty RPE(+) interns, 54 RPE(-) interns and 53 GPs participated in the study. Mean scores of RPE(+) interns were higher than those of GPs, which were in turn found to be higher than those of RPE(-) interns for all cases. The RPE(+) interns scored the highest regarding all components of rational pharmacotherapy process for all cases of both indications. However, participants in all groups had higher scores for the structured questions compared with the corresponding open ones for both diseases. Prescription analysis also revealed better results for RPE(+) interns regarding the number of drugs/prescription and treatment costs. CONCLUSION: The present study demonstrated that the final-year medical students (interns) markedly benefited from undergraduate RPE at the medical school in developing rational prescribing skills compared with their classmates from a medical school with traditional pharmacology education. Interestingly, they got higher scores than not only RPE(-) interns, but also than the GPs participating in this study, indicating the urgent need for continuous medical education programs in this field throughout the country for practicing GPs.

Decision Making↗
PubMed1998

Influence of ligation of the internal iliac veins on the venous plexuses around the sacrum.

Excessive bleeding is a significant problem during total sacrectomy. Ligation of the internal iliac veins to control bleeding from the pelvic venous plexus has been reported to be mandatory. However, despite ligation of the internal iliac veins, excessive hemorrhage from the pelvic and epidural venous plexuses is often encountered. We postulated that ligation of the internal iliac veins increases blood loss during total sacrectomy and we investigated the influence of ligation of the internal iliac veins on the pelvic and epidural venous plexuses in white rabbits. We also investigated the influence of the animal's operative position on the epidural venous pressure. Venography was performed to study the differences in blood flow patterns before and after ligation of the internal iliac veins. Without ligation, contrast medium passed into the inferior vena cava, but not into the epidural venous plexus. The epidural venous plexus was contrast-filled when the internal iliac veins were ligated. The pressure in the internal iliac veins was increased with their ligation, and decreased with ligation of the abdominal aorta. The pressure was also decreased with intentional bleeding from the epidural venous plexus, and with changing the animal's position to headdown. Ligation of the internal iliac veins leads to congestion of the pelvic venous and epidural venous plexuses. Ligation of the internal iliac arteries and positioning the animal headdown were effective ways to resolve the congestion in these venous plexuses.

Animals↗
PubMed1988

Quantitative analysis of internalization of glucagon by isolated hepatocytes.

Biochemical methods have been used to quantitate total, acid-stable and acid-labile association of (mono[125I]iodoTyr10) glucagon with rat hepatocytes in suspension to evaluate internalization of glucagon and its receptors. Internalization is inhibited by low temperature, phenylarsine oxide, and by blocking receptor binding, consistent with receptor-mediated endocytosis. Approximately 30% of the total cell-associated hormone is internalized at 30 min of incubation. The rate declines until 90 min when the internalization of glucagon ceases, although the cells remain competent to internalize asialofetuin. From 90 min to 4 h, 27% of the maximum label internalized at 30 min remains within cells. The number of cell surface receptors decreases but the affinity of those remaining is unchanged. However, 1.7-2.7 surface receptors are lost to binding for each molecule of radiolabeled glucagon internalized. Uptake occurs according to a rate constant of 0.183 min-1 (t1/2 = 3.8 min). We conclude that (i) hepatocytes internalize a finite quantity of glucagon, implying the existence of undefined regulatory mechanisms; (ii) hormone is retained for greater than 2 h within cells and may play a physiological role within cells; and (iii) both occupied and unoccupied receptors become inaccessible to extracellular hormone as internalization proceeds; rapid recycling of receptors does not occur.

Animals↗
PubMed1992

Cleavage of concatemeric DNA at the internal junction of "translocation" mutants of pseudorabies virus and inversion of their L component appear to be linked.

When pseudorabies virus (PrV) strains are grown in chicken embryo fibroblasts (CEF), variants ("translocation" mutants) arise in which there is a duplication of the leftmost sequences of the genome and their translocation in inverted orientation next to the internal inverted repeat bracketing the S component. In these variants, the UL becomes bracketed by inverted repeats and is found in two orientations relative to the Us. To study the cis-functions involved in cleavage of concatemeric DNA as well as those involved in inversion of the L component and to ascertain whether the two events are linked in the "translocation" mutants, a viral mutant (vLD68) was constructed in which the terminal 64 bp of the L component (that include sequences with homology to the pac 2 site of HSV) and the 4 terminal bp of the S component were deleted from the internal junction. Although revertants that have acquired the 68 bp at the internal junction emerge rapidly in populations of vLD68, analysis of the characteristics of this mutant revealed that: (1) the termini derived from both orientations of the L component include the 64 bp that have been deleted from the internal junction of vLD68; (2) in contrast to other "translocation" mutants, the internal junction of the vLD68 genome is not a good substrate for cleavage; (3) inversion of the L component of true vLD68 DNA does not occur or is rare; a good correlation exists in the populations of vLD68 between the proportion of revertants that have acquired an intact internal junction and the proportion of genomes with an L component that inverts. These results show that an intact internal junction in "translocation" mutants is necessary for both inversion of their L components and cleavage at their alternative internal junction. Since cleavage at the alternative junction will result in inversion of the L component, we conclude that inversion of the L component of "translocation" mutants of PrV can be attributed to cleavage of concatemeric DNA at the internal alternative junction.

Animals↗
PubMed1985

Chloroquine and primary amines inhibit the internalization of antithrombin III.trypsin complex in cultured cells.

Bovine corneal endothelial (BCE) cells have been shown to specifically bind, internalize and degrade antithrombin III (AT III).protease complexes as well as thrombin. Previous studies have indicated that chloroquine has no effect on the internalization of thrombin or other cell surface-bound ligands, but it inhibits their subsequent degradation. In contrast, the present study demonstrates the unique inhibitory effect of chloroquine on the internalization of 125I-AT III.trypsin complex by BCE cultures. Similarly, the primary amines, monodansylcadaverine and methylamine, inhibit the internalization of 125I-AT III.trypsin complex, but not the internalization of 125I-thrombin. The various amines used in this study revealed: (1) differences in the process of cellular binding and internalization between AT III.protease complex and thrombin, although the degradation of both internalized ligands proceed in an analogous manner; and (2) the unique sensitivity to chloroquine of 125I-AT III.trypsin complex internalization by cultured cells. These results might indicate that AT III.protease complexes are internalized via a distinct receptor and/or a different mechanism from thrombin.

Amines↗
PubMed1992

The effects of chronic ethanol administration on the rates of internalization of various ligands during hepatic endocytosis.

The purpose of the present study was to further characterize the ethanol-induced impairments in hepatic endocytosis. Specifically, we examined the effects of ethanol treatment on receptor-ligand internalization via the coated and noncoated pit pathways. Insulin, epidermal growth factor (EGF) and asialoorosomucoid (ASOR) were used as model ligands to study internalization by isolated hepatocytes. ASOR and EGF are thought to be internalized strictly in coated pit regions of the cell membrane, while insulin may be internalized in both coated and uncoated membrane regions. Ethanol administration for 5-7 weeks decreased internalization of ASOR and EGF while internalization of insulin was unchanged during a single round of endocytosis of surface-bound ligand. Similarly, a more quantitative measure of endocytosis, the endocytic rate constant, was decreased for EGF and ASOR but not for insulin in livers of experimental rats. When endocytosis of Lucifer yellow, a fluorescent dye known to be internalized in the cell by fluid-phase endocytosis was examined, the initial rates of dye uptake were not significantly altered by alcohol administration. These results indicate that ethanol may selectively impair internalization occurring by coated pits while it has a minimal effect on initial uptake of molecules which are internalized by noncoated membrane regions.

Animals↗
PubMed1988

A comparison of morphologic and angiographic findings in long-term internal mammary artery and saphenous vein bypass grafts.

Internal mammary artery grafts are currently considered the conduits of choice for myocardial revascularization. Comparisons of long-term morphologic changes in internal mammary artery grafts and saphenous vein grafts and correlation with premortem angiography have not been reported. Eighteen internal mammary artery and 15 saphenous vein grafts that had been in place for 12 to 118 months (mean 56) in 18 patients were removed either surgically or at necropsy and examined histologically. Premortem angiograms were performed within 1 month of histologic study in 15 of these patients. Fibrointimal proliferation was more frequent in internal mammary artery than in saphenous vein grafts 8 [( 44%] of 18 versus 4 [27%] of 15; p = NS). In contrast, atherosclerosis was common in saphenous vein grafts but was extremely rare in internal mammary artery grafts (10 of 15 versus 1 of 18; p = 0.01). A good correlation was noted between the degree of narrowing estimated by angiographic and histologic measurements in both internal mammary artery grafts (d = 0.90) and saphenous vein grafts (d = 0.71). Accelerated atherosclerosis did not occur in internal mammary artery grafts, but was common in saphenous vein grafts. Fibrointimal proliferation was commonly associated with graft narrowing in internal mammary artery grafts and may be an important factor in late graft closure. This study also confirms that internal mammary artery grafts have greater longevity compared with saphenous vein grafts.

Adult↗
PubMed2005

Comparison of saphenous vein and internal thoracic artery graft patency by coronary system.

BACKGROUND: We sought to compare saphenous vein and internal thoracic artery graft patency by coronary system. METHODS: From 1972 to 1999, 50,278 patients underwent primary coronary surgery; subsequently, 4,333 had angiography of 2,121 internal thoracic artery and 8,733 saphenous vein grafts. Longitudinal analysis was used to model graft occlusion and identify risk factors. Using the model, patency was calculated twice for each graft and compared first as if an internal thoracic artery, and second as if a saphenous vein, were used. RESULTS: Unadjusted 1-, 5-, and 10-year patency was 93%, 88%, and 90% for internal thoracic arteries and 78%, 65%, and 57% for saphenous veins. At 10 years, internal thoracic arteries were more likely than saphenous veins to be patent to left anterior descending in 99.1% of cases, to diagonals in 98.3%, to circumflex in 98.3%, to posterior descending artery in 98.5%, and to right coronary arteries in 82.5%. For right coronary arteries, saphenous vein patency was equivalent to or better than internal thoracic artery patency early after surgery. However, by 10 years, internal thoracic artery patency was better in right coronary arteries with 70% stenosis or greater. At all times after surgery and all levels of clinically important coronary stenosis, internal thoracic artery patency surpassed saphenous vein patency in grafts to the left anterior descending, diagonal, circumflex, and posterior descending arteries. CONCLUSIONS: Internal thoracic arteries demonstrate better patency than saphenous veins except when grafting moderately stenosed right coronary arteries. When bypassing right coronary arteries with less than 70% stenosis, saphenous veins may be a better choice.

Coronary Angiography↗
PubMed2006

Upper extremity arteriovenous fistulas induce modest hemodynamic effect on the in situ internal thoracic artery.

BACKGROUND: The left internal thoracic artery is the ideal conduit for coronary artery revascularization due to superior patency compared with venous grafts. The hemodynamic effects of an arterio-venous fistula on the native in situ internal thoracic artery and the potential for coronary flow steal after revascularization with the internal thoracic artery, are not well-characterized. METHODS: Fifteen chronic hemodialysis patients with functioning left upper extremity arterio-venous fistulas were evaluated with the use of transthoracic color Doppler analysis. Flow characteristics of the left and right internal thoracic arteries at baseline, with arterio-venous fistula occluded, and during hemodialysis were recorded. Peak systolic and diastolic velocities for the right and left internal thoracic arteries were calculated for each fistula state (occluded, open, and on-dialysis). One-way analysis of variance was used to compare the different means. RESULTS: Mean flow velocity calculations failed to identify any statistically significant differences between the ipsilateral and contralateral internal thoracic artery in any fistula state. In addition, mean internal thoracic flow velocities were similar between the different fistula states. CONCLUSIONS: Changes in arteriovenous fistula flow state did not significantly alter Doppler flow hemodynamics of either the ipsilateral or contralateral in-situ internal thoracic artery. Further studies of the possible effects on internal thoracic arteries used as pedicled coronary grafts may be required.

Arm↗
PubMed2006

Prospective angiographic comparison of direct, endoscopic, and telesurgical approaches to harvesting the internal thoracic artery.

BACKGROUND: The purpose of this study was to compare the quality of left internal thoracic arteries harvested by the conventional open approach versus minimally invasive videoscopic and robotic-assisted telesurgical techniques. METHODS: One hundred and fifty consecutive patients with single vessel coronary artery disease were prospectively studied. The left internal thoracic artery was harvested using three different approaches, with 50 patients consecutively assigned to each group. The off-pump coronary artery bypass (OPCAB) group underwent median sternotomy with direct visualization. The automated endoscopic system for optimal positioning (AESOP) group employed the AESOP 3000 system (Computer Motion Inc, Goleta, CA) for robotic-assisted visualization with endoscopic manual left internal thoracic artery harvesting. The Zeus group used the Zeus robotic telesurgical system (Computer Motion Inc) and internal thoracic artery harvesting was performed remotely from a surgical console. Postanastomotic left internal thoracic artery flows and day one postoperative angiography were used to assess internal thoracic artery quality and patency. RESULTS: Average left internal thoracic artery harvest times were 23 +/- 2.5, 63.3 +/- 20.3, and 66.1 +/- 17.9 minutes in the OPCAB, AESOP, and Zeus groups, respectively (p < 0.001, OPCAB vs AESOP and Zeus). Intraoperative graft flows averaged 28.1 +/- 11.9, 33.7 +/- 19.3, and 36.9 +/- 24.6 mL/minute, respectively in the OPCAB, AESOP, and Zeus groups (p = 0.317, OPCAB vs AESOP and Zeus). There was no significant angiographic difference in the patency rate of the harvested left internal thoracic arteries in the three groups (p = 0.685, overall). CONCLUSIONS: The left internal thoracic artery can be harvested safely and effectively using minimally invasive videoscopic and robotic-assisted telesurgical techniques. Although the less invasive approaches require specialized equipment and training as well as increased operative time, they offer the potential for less traumatic myocardial revascularization through smaller incisions and reduced postoperative morbidity.

Adult↗
PubMed2006

Monitoring ligand-mediated internalization of G protein-coupled receptor as a novel pharmacological approach.

Agonist activation of a G protein-coupled receptor (GPCR) results in the redistribution of the receptor protein away from the cell surface into internal cellular compartments through a process of endocytosis known as internalization. Visualization of receptor internalization has become experimentally practicable by using fluorescent reagents such as green fluorescent protein (GFP). In this study, we examined whether the ligand-mediated internalization of a GPCR can be exploited for pharmacological evaluations. We acquired fluorescent images of cells expressing GFP-labeled GPCRs and evaluated the ligand-mediated internalization quantitatively by image processing. Using beta2-adrenoceptor and vasopressin V1a receptor as model GPCRs that couple to Gs and Gq, respectively, we first examined whether these GFP-tagged GPCRs exhibited appropriate pharmacology. The rank order of receptor internalization potency for a variety of agonists and antagonists specific to each receptor corresponded well with that previously observed in ligand binding studies. In addition to chemical ligand-induced internalization, this cell-based fluorescence imaging system successfully monitored the internalization of the proton-sensing GPCR TDAG8, and that of the free fatty acid-sensitive GPCR GPR120. The results show that monitoring receptor internalization can be a useful approach for pharmacological characterization of GPCRs and in fishing for ligands of orphan GPCRs.

Animals↗
PubMed2000

Computer-based simulations enhance clinical experience of dietetics interns.

OBJECTIVE: To determine the impact of computer-based simulations on the performance of dietetics interns in initial clinical rotations. DESIGN: Interns used either a simulation program (Care Planning Simulation System CPSS[) or a computer-based tutorial (Nutrition Care Planning Tutorial NCPT[) during their orientation. Performance of these interns on nutrition care skills was evaluated during their initial clinical rotations. SUBJECTS/SETTING: Participants were 108 dietetics interns from 8 different programs. Each internship had at least 8 interns, and none of the internships awarded a graduate degree. INTERVENTION: Subjects in the experimental group completed nutrition assessment and care planning activities for 3 simulated patients. Subjects in the control group completed a tutorial on assessment and care planning. MAIN OUTCOME MEASURES: Likert scale ratings of 31 behaviors were recorded by clinical preceptors. Behavior statements were grouped into 8 categories and average ratings for each category were determined. STATISTICAL ANALYSIS: Repeated-measures analysis of variance and linear regression were used to compare performance ratings between groups. RESULTS: There were no differences in overall evaluations of the simulation and tutorial groups for the 8-week period. Interns who started clinical rotations immediately after orientation (CPSS-I and NCPT-I groups) were rated lower in all categories than those who began their clinical rotations later (CPSS-D and NCPT-D groups). Maturation and acquisition of general skills likely influenced ratings of interns with delayed clinical rotations. For most categories of behavior the rate of improvement in rating scores was greatest for interns who used CPSS. APPLICATIONS: Computer-based simulations are a promising supplement to current techniques in didactic instruction and may be useful in both didactic and practice settings. Computer-based simulations can provide more varied practice experiences to didactic students and interns in preparation for more skilled entry-level positions in dietetics.

Adult↗
PubMed2003

Radial versus right internal thoracic artery as a second arterial conduit for coronary surgery: early and midterm outcomes.

OBJECTIVE: We sought to compare early and midterm clinical outcomes in patients receiving a right internal thoracic artery or a radial artery as the second arterial conduit for myocardial revascularization. METHODS: Data prospectively collected for all patients who underwent coronary artery bypass surgery between April 1996 and May 2001 and who received both a left internal thoracic artery graft and either a right internal thoracic artery (n = 336) or a radial artery graft (n = 325) were analyzed. Patients in the radial artery group were older, with a greater body mass index, poorer ejection fraction, greater prevalence of diabetes, and higher New York Heart Association class than those in the right internal thoracic artery group. RESULTS: Odds ratios for perioperative myocardial infarction, atrial fibrillation, postoperative transfusion, and intensive care unit stay all showed a statistically significant benefit in the radial artery group compared with results in the right internal thoracic artery group (P <or=.05). Survival estimates at 18 months for patients who received right internal thoracic artery and radial artery grafts were 98.4% and 99.7%, respectively (hazard ratio, 0.25; 95% confidence interval, 0.06-1.10; P =.07). Estimates for survival free from any cardiac-related event or death in the right internal thoracic artery and radial artery groups were 92.3% and 97.8%, respectively (hazard ratio, 0.37; 95% confidence interval, 0.16-0.84; P =.02). A multivariate Cox regression model showed a stronger protective effect of a radial artery graft (hazard ratio, 0.25; 95% confidence interval, 0.12-0.51; P <.0001). CONCLUSION: Early and midterm outcomes of myocardial revascularization with 2 arterial grafts are better if the radial artery is used for the second graft rather than the right internal thoracic artery, assuming that the left internal thoracic artery is used for the first arterial graft.

Aged↗
PubMed2002

Receptor-mediated internalization of [3H]-neurotensin in synaptosomal preparations from rat neostriatum.

Following its binding to somatodendritic receptors, the neuropeptide neurotensin (NT) internalizes via a clathrin-mediated process. In the present study, we investigated whether NT also internalizes presynaptically using synaptosomes from rat neostriatum, a region in which NT1 receptors are virtually all presynaptic. Binding of [(3)H]-NT to striatal synaptosomes in the presence of levocabastine to block NT2 receptors is specific, saturable, and has NT1 binding properties. A significant fraction of the bound radioactivity is resistant to hypertonic acid wash indicating that it is internalized. Internalization of [(3)H]-NT, like that of [(125)I]-transferrin, is blocked by sucrose and low temperature, consistent with endocytosis occurring via a clathrin-dependent pathway. However, contrary to what was reported at the somatodendritic level, neither [(3)H]-NT nor [(125)I]-transferrin internalization in synaptosomes is sensitive to the endocytosis inhibitor phenylarsine oxide. Moreover, treatment of synaptosomes with monensin, which prevents internalized receptors from recycling to the plasma membrane, reduces [(3)H]-NT binding and internalization, suggesting that presynaptic NT1 receptors, in contrast to somatodendritic ones, are recycled back to the plasma membrane. Taken together, these results suggest that NT internalizes in nerve terminals via an endocytic pathway that is related to, but is mechanistically distinct from that responsible for NT internalization in nerve cell bodies.

Animals↗
PubMed1997

Internal and external anal sphincter anatomy as it relates to midline obstetric lacerations.

OBJECTIVE: To examine the anatomy of the internal and external anal sphincters in the area of midline obstetric lacerations, to gain insight into sphincter damage and repair. METHODS: The length, craniocaudal extent, and overlap of the internal and external anal sphincters in the perineal body were measured in 17 cadavers. Further anatomic observations were made in four sets of whole pelvis cross-sections taken in the sagittal, coronal, and transverse planes. During the repair of 20 acute fourth-degree lacerations, observations were made to determine the internal sphincter visibility following birth. RESULTS: The external and internal and sphincters overlap by 17.0 mm (standard deviation [SD] 6.9), with the internal sphincter lying between the external sphincter and the anal canal. The internal sphincter extends an additional 12.2 mm (SD 5.9) cranial to the proximal extent of the external sphincter, whereas the caudal margin of the internal sphincter lies 3.7 mm (SD 7.2) cranial to the distal margin of the external sphincter. In pregnant women who sustained a fourth-degree laceration, we found that the internal sphincter can be identified as a rubbery white layer adjacent to the anal submucosa lying between the external sphincter and the anal canal. CONCLUSION: The internal anal sphincter lies between the anal mucosa and the external anal sphincter and extends more than a centimeter above the cranial margin of the external sphincter, a region where it is disrupted when a fourth-degree obstetric laceration has occurred.

Aged↗