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Exogenous tau RNA is localized in oocytes: possible evidence for evolutionary conservation of localization mechanisms.

The multistep pathway leading to intracellular RNA localization is known to involve cis-acting signals in targeted mRNAs, which are presumably recognized by specific RNA-binding proteins and interact with a functional cytoskeleton. Tau RNA is localized to the proximal hillock of rat axons, and this movement requires intact microtubules. Because Xenopus oocytes demonstrate a clear polarity involving microtubule-mediated RNA localization, we have studied the distribution of tau RNA injected into oocytes. We find that a fragment from the 3'-untranslated region of tau RNA is localized to the vegetal cortex of stage III/IV oocytes in a distribution indistinguishable from Vg1 RNA, a vegetally localized oocyte mRNA. A fragment from the tau RNA coding region, however, is homogeneously distributed in oocytes. Tau RNA contains a functional binding site for Vg1 RBP, a Xenopus microtubule-associated protein that binds vegetally localized oocyte RNAs with high affinity, and this binding correlates with vegetal localization ability. The present studies demonstrate, for the first time, localization of heterologous RNA in oocytes. Given the role of Vg1 RBP as a mediator of specific RNA-microtubule interactions, these results are strong evidence that Vg1 RBP is involved in the vegetal localization of RNAs in oocytes and raise the intriguing possibility of the existence of proteins with similar function in neurons.

Actins↗

Improved dipole localization using local mesh refinement of realistic head geometries: an EEG simulation study.

A systematic evaluation of dipole localization accuracy using the boundary element method is presented. EEG simulations are carried out with dipoles located in the right parietal and temporal regions of the head. Uniformly meshed and locally refined head models are considered in both spherical and realistic geometries. An initial study determines the influence upon the localization accuracy of the dipole depth below the brain surface, of its orientation (radial and tangential), and of the global and local mesh densities. Simulated potential data are computed analytically in the spherical case, and numerically using a very fine (locally refined) model in the realistic case. Results in both geometries show that in order to get localization errors of about 2-4 mm, uniformly meshed models may be used for dipoles located at depths greater than 20 mm, whereas locally refined models should be used for shallower dipoles. Two other studies show how the localization accuracy depends upon the size of the local refinement area and upon the number of electrodes (19, 32, 63). Results show that a large number of electrodes brings significant improvements, especially for shallow and tangential dipoles.

Brain↗

Estimation of local scale dispersion from local breakthrough curves during a tracer test in a heterogeneous aquifer: the Lagrangian approach.

The local scale dispersion tensor, Dd, is a controlling parameter for the dilution of concentrations in a solute plume that is displaced by groundwater flow in a heterogeneous aquifer. In this paper, we estimate the local scale dispersion from time series or breakthrough curves, BTCs, of Br concentrations that were measured at several points in a fluvial aquifer during a natural gradient tracer test at Krauthausen. Locally measured BTCs were characterized by equivalent convection dispersion parameters: equivalent velocity, v(eq)(x) and expected equivalent dispersivity, [lambda(eq)(x)]. A Lagrangian framework was used to approximately predict these equivalent parameters in terms of the spatial covariance of log(e) transformed conductivity and the local scale dispersion coefficient. The approximate Lagrangian theory illustrates that [lambda(eq)(x)] increases with increasing travel distance and is much larger than the local scale dispersivity, lambda(d). A sensitivity analysis indicates that [lambda(eq)(x)] is predominantly determined by the transverse component of the local scale dispersion and by the correlation scale of the hydraulic conductivity in the transverse to flow direction whereas it is relatively insensitive to the longitudinal component of the local scale dispersion. By comparing predicted [lambda(eq)(x)] for a range of Dd values with [lambda(eq)(x)] obtained from locally measured BTCs, the transverse component of Dd, DdT, was estimated. The estimated transverse local scale dispersivity, lambda(dT) = DdT/U1 (U1 = mean advection velocity) is in the order of 10(1)-10(2) mm, which is relatively large but realistic for the fluvial gravel sediments at Krauthausen.

Chemical Phenomena↗

Mechanism of adenylate kinase. Is there a relationship between local substrate dynamics, local binding energy, and the catalytic mechanism?

Adenylyl (beta,gamma-methylene)diphosphonic acid (AMPPCP) labeled with deuterium at the adenine ring ([8-2H]AMPPCP) and at the beta,gamma-methylene group (AMPPCD2P), as well as adenosine 5'-monophosphate labeled at the adenine ring ([8-2H]AMP), was synthesized and used for deuterium nuclear magnetic resonance (NMR) determination of effective correlation times (tau c) of the free nucleotide and the complexes with adenylate kinase (AK). Extensive and rigorous control experiments and theoretical analysis were performed to justify the validity of the experimental approaches, particularly the fast exchange condition, and the reliability of the tau c values obtained. For the free nucleotide, the results suggest that the phosphonate group of free AMPPCP possesses appreciable local mobility relative to the adenine ring and that complexation with Mg2+ greatly reduced such a local mobility. For the complexes with AK, effective tau c values of 7, 15, 28, 28, and 27 ns were obtained for AMPPCD2P, MgAMPPCD2P, [8-2H]AMPPCP, Mg[8-2H]AMPPCP, and [8-2H]AMP, respectively. These results suggest that the adenine ring of substrates is rigidly bound in all cases, that the phosphonate chain of AMPPCP possesses considerable local mobility, and that Mg2+ reduces such local mobility but does not totally immobilize it. The local dynamics of the analogues bound to AK was correlated with local binding energies for the binding of MgAMPPCP and MgATP to AK estimated from the binding studies by proton NMR and other techniques, in conjunction with the binding theory of Jencks [Jencks, W. P. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 4046-4050]. The results suggest that no general correlation exists between the local rigidity of portions of a bound substrate and the corresponding (ground state) local binding energy contributed by these portions. In particular, the adenosine moiety contributes little to the binding energy despite the fact that the adenine ring is rigidly bound; the triphosphate (PPPi) moiety behaves oppositely; Mg2+ immobilizes the triphosphate chain but does not enhance binding. Finally, isomers of the substitution-inert beta,gamma-bidentate Cr(III) complexes of adenosine 5'-triphosphate (CrATP) were used to probe two unresolved catalytic problems implicitly related to the local mobility of the phosphonate chain of AMPPCP in the AK-MgAMPPCP complex. The first problem concerns the result of electron paramagnetic resonance (EPR) studies that (Rp)- but not (Sp)-[beta-17O]ATP caused a line broadening in the Mn(II) EPR spectrum of the AK-MnATP complex [Kalbitzer, H. R., Marquetant, R., Connolly, B. A., & Goody, R. S. (1983) Eur. J. Biochem. 133, 221-227].(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

Regional enrichment of local assemblages is robust to variation in local productivity, abiotic gradients, and heterogeneity.

Theory predicts that the effects of regional richness on the richness of local communities may depend on the productivity, resource availability, and/or heterogeneity of local sites. Using the wetland plant communities of 50 independent streams as 'regions', we tested whether: (1) local richness in 1-m(2) quadrats and 50-m stream segments was positively related to regional richness, even after environmental influences were considered; and (2) the effect of regional richness would interact with the effects of biomass, soil moisture, and/or heterogeneity on local richness. In models that explained up to 88% of variation in local richness, we found that richness at both local scales was positively related to regional richness, and that regional richness did not interact with any of the environmental gradients that also shaped local richness. We conclude that species availability from the regional pool may consistently enrich local communities, even while other constraints on local richness operate.

Biomass↗

Dispersal frequency affects local biomass production by controlling local diversity.

Dispersal is a major factor regulating the number of coexisting species, but the relationship between species diversity and ecosystem processes has mainly been analysed for communities closed to dispersal. We experimentally investigated how initial local diversity and dispersal frequency affect local diversity and biomass production in open benthic microalgal metacommunities. Final local species richness and local biomass production were strongly influenced by dispersal frequency but not by initial local diversity. Both final local richness and final local biomass showed a hump-shaped pattern with increasing dispersal frequency, with a maximum at intermediate dispersal frequencies. Consequently, final local biomass increased linearly with increasing final richness. We conclude that the general relationship between richness and ecosystem functioning remains valid in open systems, but the maintenance of ecosystem processes significantly depends on the effects of dispersal on species richness and local interactions.

Animals↗

Factors affecting survival following local, regional, or distant recurrence from localized melanoma.

BACKGROUND AND OBJECTIVES: Approximately one third of all melanoma patients will experience disease recurrence. Factors that affect patient survival following local, regional, or distant first recurrences of localized melanoma are the subject of this investigation. METHODS: Survival times for a total of 1,085 first recurrences from 4,568 localized melanoma patients were examined in relationship to patient and disease factors by Cox regression. Nearly half (48.8%) of all first recurrences were regional, 21.8% were local, and 29.4% were distant recurrences. RESULTS: Survival following recurrence differed significantly by site of recurrence (local, regional, or distant; P < 0.0001). Within each site, the median survival time did not differ by time of recurrence following diagnosis. Significant tumor factors for survival following local recurrence included tumor thickness (P = 0.0263) and lesion location (P < 0.0001). For regional recurrences, survival was significantly related to ulceration (P = 0.0105) and whether the recurrence was combined with a local recurrence (P = 0.0429). Survival following distant metastasis was related to number of distant sites (P < 0.0001) and whether a visceral site was involved (P < 0.0001). CONCLUSIONS: Patient and tumor characteristics predict survival following recurrence. Regardless of disease-free interval, long-term follow-up of melanoma patients is necessary. Patients experiencing distant metastasis have the shortest median survival time compared to patients experiencing local or regional recurrences.

Disease-Free Survival↗

Local recurrence after breast conservation therapy for early stage breast carcinoma: detection, treatment, and outcome in 266 patients. Dutch Study Group on Local Recurrence after Breast Conservation (BORST).

BACKGROUND: Controversy exists concerning the roles of mammography and physical examination in the detection of local recurrence after conservation therapy for breast carcinoma. In addition, the prognostic factors for and optimal treatment of patients with local recurrence are uncertain. METHODS: At eight radiotherapy institutes, two cancer institutes, and one surgical clinic in the Netherlands, regular follow-up of patients who underwent breast conservation therapy between 1980 and 1992 identified 266 patients with local recurrence in the breast. These patients exhibited no clinical signs of distant metastases at the time of diagnosis of the local recurrence. Data on the method of detection were available for 189 patients (72%). Local recurrence was diagnosed by mammography alone in 47 cases (25%). Of all patients, 85% underwent salvage mastectomy, 8% underwent local excision, 4% received systemic treatment only, and 3% remained untreated. Specimens of the primary tumor were available for review from 238 of the 266 patients (89%). RESULTS: Local recurrences detected by mammography alone were smaller than those detected by physical examination (P = 0.04). At 5 years from the date of salvage treatment, the overall survival rate for all 266 patients was 61% (95% confidence interval [CI], 55-67%), and the distant recurrence free survival rate was 47% (95% CI, 40-53%). For the 25 patients with noninvasive recurrence, these figures were 95% and 94%, respectively. Skin involvement, the extent of recurrence (< or = 10 mm vs. >10 mm), and both lymph node status and histologic grade of the primary disease were strong predictors for distant metastases in patients with invasive recurrence. CONCLUSIONS: Patients with invasive local recurrence more than 1 cm in size are at a substantial risk for distant disease. The better distant disease free survival for patients with recurrence measuring 1 cm or less may indicate that early detection can improve the treatment outcome. Recurrence with skin involvement should be considered generalized disease.

Adult↗

Effect of awake Carotid Endarterectomy under local anaesthesia on peri-operative blood pressure: blood pressure is normalised when carotid stenosis is treated under local anaesthesia.

BACKGROUND: Carotid Endarterectomy can be performed under local, regional or general anaesthesia. One of the most important effects of the type of anaesthetic used is on the systemic blood pressure. Although variations in blood pressure during and following carotid endarterectomy have been studied previously, the effects of awake carotid endarterectomy under local anaesthesia on blood pressure and its comparison with similar procedures under similar types of anaesthesia have not. METHODS: Peri-operative blood pressure measurements were collected from the records of 25 consecutive patients for each of the following five procedures; Carotid Endarterectomy under general anaesthesia (CEAGA), Anterior Cervical Discectomy and Fusion under general anaesthesia (ACDF), Cerebral Angiography under local anaesthesia (ANG), Carotid Endarterectomy patients under local anaesthesia who were symptomatic (CEALAS) and Carotid Endarterectomy patients under local anaesthesia who were asymptomatic (CEALAA). The recordings were then analysed to find out if there were any clinically significant variations in peri-operative blood pressure. FINDINGS: There is a significant and consistent difference when the pre-operative value was compared with the 4 hour and 24 hour post-operative recordings between the local and general anaesthetic groups for carotid endarterectomy. Carotid endarterectomy reduces the systolic and diastolic blood pressures post-operatively when performed under local anaesthesia and only the diastolic pressure was reduced when performed under general anaesthesia. CONCLUSION: The study provides evidence about the effect of carotid endarterectomy on the systemic blood pressure and its variations when performed under different types of anaesthesia. There is significant post-operative reduction in both the systolic and diastolic blood pressure values and the intraoperative fluctuation is minimal when local anaesthesia is used. Further studies are required to find out how this affects the long-term blood pressure and clinical outcome of the patient.

Anesthesia, General↗

Effects of local anaesthesia or local anaesthesia plus a non-steroidal anti-inflammatory drug on the acute cortisol response of calves to five different methods of castration.

The cortisol response of calves to different methods of castration (ring, band, surgical, clamp) with or without local anaesthetic, or local anaesthetic plus a non-steroidal anti-inflammatory drug were recorded. All methods of castration caused a significant cortisol response and by inference pain and distress. Band castration caused a greater cortisol response than ring castration but the responses were eliminated by local anaesthetic. The cortisol response to surgical castration, by traction on the spermatic cords or by cutting across them with an emasculator, was not diminished by local anaesthetic but when ketoprofen was given with local anaesthetic the cortisol response was eliminated. Local anaesthetic did reduce the behavioural response to cutting the scrotum and handling the testes. Clamp castration caused the smallest cortisol response which was reduced or eliminated by local anaesthetic or local anesthetic plus ketoprofen respectively, but this method of castration was not always successful.

Anesthetics, Local↗

Local-regional control of recurrent breast carcinoma after mastectomy: does hyperfractionated accelerated radiotherapy improve local control?

PURPOSE: Hyperfractionated, accelerated radiotherapy (HART) has been advocated for patients with local-regionally recurrent breast cancer because it is believed to enhance treatment effects in rapidly proliferating or chemoresistant tumors. This report examines the value of HART in patients with local-regionally recurrent breast cancer treated with multimodality therapy. METHODS AND MATERIALS: The study included 148 patients with local-regionally recurrent breast cancer after mastectomy, who were treated with definitive local irradiation and systemic therapy consisting of either tamoxifen, cytotoxic chemotherapy, or both, along with excision of the recurrent tumor when possible. Patients with distant metastases were excluded, except for two patients with ipsilateral supraclavicular nodal metastases. Patients received comprehensive irradiation to the chest wall and regional lymphatics to a median dose of 45 Gy, with a boost to 60 Gy to areas of recurrence. Sixty-eight patients (46%) were treated once daily at 2 Gy/fraction (fx), and 80 (54%) were treated twice daily at 1.5 Gy/fx. Forty-eight patients (32%), who had palpable gross disease that was unresponsive to systemic therapy and/or unresectable, were irradiated. The median follow-up time of surviving patients was 78 months. RESULTS: Overall actuarial local-regional control (LRC) rates at 5 and 10 years were 68% and 55%, respectively. Five- and ten-year actuarial overall survival (OS) and disease-free survival (DFS) rates were 50% and 35%, 39% and 29%, respectively. Univariate analysis revealed that LRC was adversely affected by 1. advanced initial American Joint Committee on Cancer (AJCC) stage (p = 0.001), 2. clinically evident residual disease at time of treatment (p < 0.0001), 3. more than three positive nodes at initial mastectomy (p = 0.014), 4. short interval from mastectomy to recurrence (< 24 months, p = 0.0007), 5. nuclear grade (III vs. I or II, p = 0.045), and 6. number of recurrent nodules (1 vs. > 1, p = 0.02). Patient age at time of recurrence (< 40 vs. > or = 40 years), recurrence location on the chest wall, estrogen receptor status, progesterone receptor status or menopausal status did not adversely affect LRC. On multivariate analysis, only clinically evident residual disease at the time of treatment and short interval from mastectomy to recurrence remained significant. When once-a-day irradiation was compared to the twice-a-day schedule, no significant differences were seen in LRC (67% vs. 68%), OS (47% vs. 52%), or DFS (42% vs. 36%) for the entire group of patients at 5 years. Pairwise comparison of the two fractionation schedules in each of the adverse outcome subgroups identified above showed no clinically significant differences in LRC at 5 years. For the 48 patients who began radiotherapy with measurable gross local recurrence, the complete response rate to radiotherapy was 73%, with no difference seen between the two fractionation schedules. The incidence of acute and chronic radiation-related complications was similar in both treatment groups. CONCLUSIONS: Hyperfractionated accelerated radiotherapy, although well tolerated by patients with local-regionally recurrent breast cancer, did not result in superior local-regional control rates when compared to daily fractionated regimens. Alternative strategies, such as dose escalation or chemoradiation, may be required to improve control.

Adolescent↗

Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Dutch Study Group on local Recurrence after Breast Conservation (BORST)

The purpose of this study was to determine which histological factors are associated with an increased risk for local recurrence in the breast after breast-conserving therapy for early breast cancer (TNM stage I and II) and whether risk patterns vary according to menopausal status and type of local recurrence. Through complete follow-up of the patients of eight regional radiation oncology departments, two cancer institutes and one surgical clinic in The Netherlands, 360 patients were identified with local recurrence in the breast after having received breast-conserving therapy (local tumour excision, axillary dissection and irradiation of the whole breast and a boost to the tumour bed) during the 1980s. For each case, two controls with a follow-up of similar duration without local recurrence were randomly selected. Histological slides of the primary tumour were reviewed. Among premenopausal patients the risk of recurrence for those younger than 35 years was significantly higher than that for premenopausal patients of 45 years or older (relative risk (RR) 2.9; 95% confidence interval (95% CI) 1.3-6.6, P < 0.05). The risk of recurrence at or near the site of the primary tumour was most significantly increased for patients with high grade extensive intraductal component (EIC) adjacent to the primary tumour (RR 4.1; 95% CI 1.7-9.8, P < 0.01). Microscopic margin involvement was an important risk indicator for diffuse recurrence and recurrence in the skin of the breast, especially in the presence of vascular invasion (RR 25; 95% CI 4.0-150, P < 0.001). To prevent local recurrence at or near the site of the primary tumour, local excision with a 1-2 cm margin of healthy tissue and a 15 Gy boost seemed adequate local treatment for patients with well differentiated EIC. In contrast, a wider surgical margin, a higher boost dose or mastectomy should be considered for patients with poorly differentiated EIC. Microscopic margin involvement in the presence of vascular invasion significantly increases the risk of diffuse recurrence or recurrence in the skin.

Adult↗

Three new active cisplatin-containing combinations in the neoadjuvant treatment of locally advanced and locally recurrent breast carcinoma: a randomized phase II trial.

We designed three new four-drug cisplatin-containing combinations and evaluated their activity in a randomized phase II study including patients with locally advanced (stage III) and locally recurrent breast carcinoma. All combinations included methotrexate (M) on day 1 and cisplatin (P) on day 2 (MVAC-like combinations) and differed from one another by the addition of Epirubicin (Epi), Vincristine (V), Etoposide (E), Mitomycin (Mi). Based on the administered agents, they were named MPEMi, MPEpiE, MPEpiV. The combinations were randomly assigned to 101 patients, 57 with locally advanced and 44 with locally recurrent breast carcinoma. Response was evaluated after 4 cycles. The complete response (CR) rates were 7% and 43% and the CR plus partial response (PR) rates were 84% and 89% in locally advanced and in locally recurrent disease, respectively. In locally advanced disease, a pathologic CR (pCR) was assessed in seven of 57 patients (12%). There were no significant differences among the three combinations. The toxicities were at times severe, but generally tolerable, as demonstrated by the high cumulative doses of the drugs received by the patients. In conclusion, these three innovative chemotherapy regimens induced high CR plus PR rates in the neoadjuvant treatment of stage III and of locally recurrent breast carcinoma, and a high rate of pCR in stage III disease. These regimens warrant testing in phase III trials.

Adult↗

Ubc9 interacts with a nuclear localization signal and mediates nuclear localization of the paired-like homeobox protein Vsx-1 independent of SUMO-1 modification.

Vsx-1 is a paired-like:CVC homeobox gene whose expression is linked to bipolar cell differentiation during zebrafish retinogenesis. We used a yeast two-hybrid screen to identify proteins interacting with Vsx-1 and isolated Ubc9, an enzyme that conjugates the small ubiquitin-like modifier SUMO-1. Despite its interaction with Ubc9, we show that Vsx-1 is not a substrate for SUMO-1 in COS-7 cells or in vitro. When a yeast two-hybrid assay is used, deletion analysis of the interacting domain on Vsx-1 shows that Ubc9 binds to a nuclear localization signal (NLS) at the NH(2) terminus of the homeodomain. In SW13 cells, Vsx-1 localizes to the nucleus and is excluded from nucleoli. Deletion of the NLS disrupts this nuclear localization, resulting in a diffuse cytoplasmic distribution of Vsx-1. In SW13 AK1 cells that express low levels of endogenous Ubc9, Vsx-1 accumulates in a perinuclear ring and colocalizes with an endoplasmic reticulum marker. However, NLS-tagged STAT1 protein exhibits normal nuclear localization in both SW13 and SW13 AK1 cells, suggesting that nuclear import is not globally disrupted. Cotransfection of Vsx-1 with Ubc9 restores Vsx-1 nuclear localization in SW3 AK1 cells and demonstrates that Ubc9 is required for the nuclear localization of Vsx-1. Ubc9 continues to restore nuclear localization even after a C93S active site mutation has eliminated its SUMO-1-conjugating ability. These results suggest that Ubc9 mediates the nuclear localization of Vsx-1, and possibly other proteins, through a nonenzymatic mechanism that is independent of SUMO-1 conjugation.

Amino Acid Sequence↗

Safety, accuracy, and diagnostic yield of needle localization biopsy of the breast performed using local anesthesia.

BACKGROUND: In changing our technique to performing needle localization breast biopsies (NLBB) using local anesthesia in an outpatient setting, we investigated whether or not our complication rates with local anesthesia were acceptable when compared with complications from a cohort of biopsies of the breast performed for palpable masses. We were also interested in determining whether or not our rate of missed biopsies was within acceptable ranges. STUDY DESIGN: Complications occurring in 283 patients who underwent 301 NLBB using local anesthesia between 1983 and 1991 were compared with complications occurring after excision of 249 palpable masses of the breast excised using local anesthesia during this period. RESULTS: Complications associated with NLBB were missed lesions, six (1.99 percent) of 301; hematoma, 12 (3.99 percent) of 301; abscess, three (0.99 percent) of 301; seroma, one (0.33 percent) of 301, and wound separation, two (0.66 percent) of 301, for a total of 24 complications (7.96 percent). These rates were not statistically different from the rates of complication after biopsies of palpable lesions using local anesthesia (p < 0.49). The 301 NLBB revealed 87 carcinomas (28.9 percent); 50 invasive and 37 in situ. Of the nonpalpable carcinomas, 43 percent were in situ. Only 11 percent carcinomas, 43 percent were in situ. Only 11 percent of the palpable lesions were in situ (p < 0.001). Forty-four patients with nonpalpable invasive carcinoma had a 25 percent rate of positive axillary lymph nodes. CONCLUSIONS: Needle localization breast biopsies can be performed using local anesthesia exclusively with less than a 2 percent chance of missed lesions and complication rates similar to those associated with biopsies of palpable lesions. The biology of these lesions varies. Although there is a high rate of in situ carcinoma, there is a significant rate of node positivity in the patients with nonpalpable invasive carcinoma.

Adolescent↗

Localized amyloidosis of the parotid gland: a case report and review of the localized amyloidosis of the head and neck.

BACKGROUND: Localized amyloidosis in the head and neck is a rare and benign process. METHODS: We present the first case report in the literature of localized amyloidosis of the parotid glands and also comprehensively review the literature regarding localized amyloidosis of the head and neck. RESULTS: Amyloidosis affecting the head and neck region is uncommon and is mostly in the form of localized amyloidosis. Larynx is the commonest site of involvement and accounts for 0.2% to 0.5% of benign laryngeal tumors. Laryngeal involvement could be either diffuse subepithelial deposition or discrete tumor nodules. Although localized amyloidosis occurs much more frequently in the oral cavity and pharynx, only seven cases of nasopharyngeal amyloidosis and eight cases of nasal septum amyloidosis have been reported. There is no documentation to suggest that localized amyloidosis can progress to systemic amyloidosis. Local surgical excision is the treatment of choice for laryngeal amyloidosis and laser excision is probably the best. CONCLUSION: While localized amyloidosis of the head and neck region is rare, it should be recognized, understood, evaluated, and properly treated.

Aged↗

Effects of local restriction of evaporation and moderate local ventilation on thermoregulatory responses in exercising humans.

Ten healthy young men participated in two series of three trials: series 1 (C1) with, or without, local restriction of evaporation (either on the trunk or on the legs) and series 2 (C2) with, or without, local moderate nitrogen ventilation (40 l.min-1) under an impermeable garment (trunk or leg ventilation). After 60-min rest in a thermoneutral environment, the subjects exercised in a warm environment [30 degrees C, 47% relative humidity (rh) during C1 and 29% rh during C2] on a cycle ergometer for 60 min at 70 W during C1 or at 60 W during C2. During C1, local covering with plastic foil did not increase internal temperature, but increased the mean skin temperature with a higher effect in the case of leg restriction. The trunk skin temperature was affected by the leg covering while the leg skin temperature was not changed by the trunk covering. Only the local sweat rate of the trunk was increased by the two restriction conditions. During C2, internal temperature was decreased by local ventilation while mean skin temperature was reduced only by trunk ventilation. The local ventilation affected only trunk skin temperature with a greater decrease during trunk ventilation. Trunk ventilation did not influence the skin temperature of the legs while ventilation of the legs decreased trunk skin temperature. In addition, leg ventilation decreased the sweat rate of the legs. The impermeable suit worn during C2 led to a greater physiological strain compared to the plastic film worn during C1 even with local ventilation under the impermeable garment. As expected, limiting sweat evaporation led to an increase in physiological strain. Microclimate ventilation at a rate of 40 l.min-1 was not sufficient to allow total heat dissipation but allowed 60-min exercise in a warm environment to be completed without excessive heat accumulation. It would appear that ventilation of the trunk locally was the best solution because of the smaller increase in skin temperature and higher sweating capacity of the trunk.

Adult↗

The localization of porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus of infected cells and identification of a potential nucleolar localization signal sequence.

The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) possesses two regions in the N-terminal half of the protein that are enriched in basic amino acids. Presumably, these basic regions are important for packaging the RNA genome within the nucleocapsid of the virus. The PSORT computer program identified the same regions as nuclear localization signal (NLS) sequence motifs. N protein localization to the nucleus of infected MARC-145 and porcine pulmonary macrophages was observed following staining with SDOW-17 and SR-30 anti-N monoclonal antibodies. Furthermore, the co-localization of SR-30 antibody with human ANA-N autoimmune serum identified the nucleolus as the primary site for N protein localization within the nucleus. The localization of the N protein in the absence of infection was studied by following fluorescence in MARC-145 cells transfected with a plasmid, which expressed the nucleocapsid protein fused to an enhanced green fluorescent protein (N-EGFP). Similar to infected cells, N-EGFP localized to the cytoplasm and the nucleolus. Results following the transfection of cells with pEGFP fused to truncated portions of the N gene identified a region containing the second basic stretch of amino acids as the nucleolar localization signal (NoLS) sequence. Another outcome following transfection was the rapid disappearance of cells that expressed high levels of N-EGFP. However, cell death did not correlate with localization of N-EGFP to the nucleolus.

Amino Acid Sequence↗