Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “elevational migration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,333 records · Page 74Linked to original sources
PubMed1990

Role of neutrophils in the intestinal alterations associated with thermal injury.

We have examined the role of neutrophils in the alterations observed in the intestines of rats subjected to 40 per cent surface area scald injury. Histologically, there was no evidence of neutrophilia in the intestinal tissue, and myeloperoxidase activity in mucosal scrapings was not elevated. The distribution of labelled human neutrophils injected into the burned rats showed no enhancement of uptake in the intestines, although there was increased uptake by the lung. The present data suggest that neutrophil migration may not play a role in the alterations in small intestinal function and morphology seen in burn trauma in the rat, but may be a factor in lung damage associated with thermal injury.

Acute Disease↗
PubMed2003

Lead transformation and distribution in the soils of shooting ranges in Florida, USA.

The use of lead bullets and shot at shooting ranges is under increasing scrutiny as a potentially significant source of Pb pollution. This study assessed Pb contamination in the soils of two shooting ranges (TRR and MPR) in Florida. Soil samples were collected from the two ranges and analyzed for total Pb to determine Pb contamination. Selected spent bullets and berm soil samples were mineralogically characterized to identify Pb transformation. Total Pb in the range soils was significantly elevated with the highest (up to 4.84% by weight) in the berm soils. Most soils failed the synthetic precipitation leaching procedure (SPLP) test. Also, at the MPR shooting range, a substantial amount of Pb migrated down in the subsurface soil, possibly due to the enhanced solubilization of organic Pb complexes at alkaline pH, whereas high cation exchange capacity of the profile soil may be responsible for Pb retention in the subsoil. The weathering products on the surface of the spent bullets were predominantly hydrocerussite [Pb(3)(CO(3))(2)(OH)(2)] and cerussite (PbCO(3)). Hydrocerussite was mainly found in the MPR range soils, whereas Pb was transformed into hydroxypyromorphite [Pb(5)(PO(4))(3)OH] in the TRR range soils because of the presence of more P. Sequential extraction and lead activity ratio modeling showed that the soil Pb solubility was controlled by Pb carbonate minerals in the MPR shooting range, and by less soluble Pb phosphate minerals in the TRR shooting range. This research suggests that it is important to develop and implement efficient management practices to minimize adverse impacts of Pb at shooting ranges. Phosphate-induced Pb immobilization may be an effective alternative for reducing Pb mobility in the shooting range soils.

Journal Article↗
PubMed2006

RabGEF1 regulates stem cell factor/c-Kit-mediated signaling events and biological responses in mast cells.

We recently reported that RabGEF1 is a negative regulator of high-affinity Fc receptor for IgE (Fc epsilonRI)-dependent mast cell activation and that mice lacking RabGEF1 develop severe skin inflammation and increased numbers of dermal mast cells. To better understand how RabGEF1 can regulate signaling events and biological responses in mast cells, we examined the responses of bone marrow-derived cultured mast cells (BMCMCs) from wild-type (+/+) and Rabgef1 knockout (-/-) mice after stimulation with the c-Kit ligand, stem cell factor (SCF), an important regulator of mast cell development, survival, proliferation, and activation. We found that RabGEF1-deficient mast cells exhibited enhanced and prolonged activation of Ras and extracellular regulated kinase, and significantly elevated IL-6 secretion, after stimulation with SCF. SCF-induced activation of c-Jun N-terminal kinase was increased in Rabgef1-/- BMCMCs, but without corresponding significant increases in SCF-induced migration or adhesion. SCF-mediated activation of the survival-enhancing kinase, Akt, also was increased in Rabgef1-/- BMCMCs, and these cells had a survival advantage over their +/+ counterparts in vitro. Despite enhanced Ras activation in the absence of RabGEF1, SCF-induced proliferation was lower in Rabgef1-/- BMCMCs compared with their +/+ counterparts. Finally, we found that c-Kit internalization was delayed in the absence of RabGEF1, probably reflecting a positive role for RabGEF1 in the regulation of endocytic events, and that infection of Rabgef1-/- BMCMCs with a wild-type RabGEF1 lentiviral construct normalized c-Kit internalization to the levels seen in +/+ BMCMCs. Thus, RabGEF1 plays a critical role in the regulation of SCF/c-Kit-mediated signaling events and biological responses in mast cells.

Animals↗
PubMed2006

Adoptive immunotherapy induces CNS dendritic cell recruitment and antigen presentation during clearance of a persistent viral infection.

Given the global impact of persistent infections on the human population, it is of the utmost importance to devise strategies to noncytopathically purge tissues of infectious agents. The central nervous system (CNS) poses a unique challenge when considering such strategies, as it is an immunologically specialized compartment that contains a nonreplicative cell population. Administration of exogenously derived pathogen-specific memory T cells (referred to as adoptive immunotherapy) to mice burdened with a persistent lymphocytic choriomeningitis virus (LCMV) infection from birth results in eradication of the pathogen from all tissues, including the CNS. In this study, we sought mechanistic insights into this highly successful therapeutic approach. By monitoring the migration of traceable LCMV-specific memory CD8+ T cells after immunotherapy, it was revealed that cytotoxic T lymphocytes (CTLs) distributed widely throughout the CNS compartment early after immunotherapy, which resulted in a dramatic elevation in the activity of CNS antigen-presenting cells (APCs). Immunotherapy induced microglia activation as well as the recruitment of macrophages and dendritic cells (DCs) into the brain parenchyma. However, DCs emerged as the only CNS APC population capable of inducing memory CTLs to preferentially produce the antiviral cytokine tumor necrosis factor-alpha, a cytokine demonstrated to be required for successful immunotherapeutic clearance. DCs were also found to be an essential element of the immunotherapeutic process because in their absence, memory T cells failed to undergo secondary expansion, and viral clearance was not attained in the CNS. These experiments underscore the importance of DCs in the immunotherapeutic clearance of a persistent viral infection and suggest that strategies to elevate the activation/migration of DCs (especially within the CNS) may facilitate pathogen clearance.

Animals↗
PubMed2005

Histidine-rich glycoprotein: A novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems.

Histidine-rich glycoprotein (HRG) is an abundant plasma glycoprotein that has a multidomain structure, interacts with many ligands, and has been shown to regulate a number of important biological processes. HRG ligands include Zn(2+) and haem, tropomyosin, heparin and heparan sulphate, plasminogen, plasmin, fibrinogen, thrombospondin, IgG, FcgammaR and complement. In many cases, the histidine-rich region of the molecule enhances ligand binding following interaction with Zn(2+) or exposure to low pH, conditions associated with sites of tissue injury or tumour growth. The multidomain nature of HRG indicates that it can act as an extracellular adaptor protein, bringing together disparate ligands, particularly on cell surfaces. HRG binds to most cells primarily via heparan sulphate proteoglycans, binding which is also potentiated by elevated free Zn(2+) levels and low pH. Recent reports have shown that HRG can modulate angiogenesis and additional studies have shown that it may regulate other physiological processes such as cell adhesion and migration, fibrinolysis and coagulation, complement activation, immune complex clearance and phagocytosis of apoptotic cells. This review outlines the molecular, structural, biological and clinical properties of HRG as well as describing the role of HRG in various physiological processes.

Animals↗
PubMed1995

Differential mRNA expression of insulin-like growth factor system during renal injury and hypertrophy.

The cellular effects of insulin-like growth factor I (IGF-I) are modified by a family of binding proteins (IGFBPs) that act as reservoirs in serum for the growth factor and are produced locally by tissues, including the kidney. Because regulation of these proteins may influence renal repair, either directly or by their interactions with IGF-I, we studied gene expression during the recovery from renal failure induced by folic acid and during the compensatory increase in renal function following uninephrectomy (UNX). Expression of IGF-I, the IGF-I receptor (IGF-IR), and all six IGFBPs was detected using an ribonuclease protection assay. IGFBP-5 was the most abundant binding protein mRNA present in kidney, whereas IGFBP-2 and -6 were the least abundant. During regeneration following folic acid-induced acute renal failure, IGF-I, IGFBP-3, and IGFBP-5 mRNAs declined in abundance approximately two- to threefold. On the other hand, IGF-IR, IGFBP-1, and IGFBP-2 were increased (approximately 2-, 6-, and 6-fold, respectively) in the first 24 h. IGFBP-1 mRNA remained elevated for at least 3 days. Despite the known increase in cellular RNA content following UNX, little difference in specific expression of mRNAs was observed. Because IGFBP-1 has been shown to stimulate cell migration and has previously been localized to the distal nephron, the site of greatest injury in the folic acid model, these data are compatible with the notion that this protein may function either directly to affect cellular repair or act as a reservoir for IGF-I under conditions of cellular damage.

Animals↗
PubMed2006

Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio.

BACKGROUND: The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation. METHODS: ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on TNF-alpha induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days. RESULTS: ICAM-1: In human venous endothelial cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002-2 microg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 microg/ml (p < 0.05), 0.002 microg/ml (p < 0.001), and 0.2 microg/ml (p < 0.05). Proliferation: Small but statistically significant antiproliferative effects of abciximab were detected after incubation of HUVEC (0.02 and 2.0 microg/ml; p = 0.01 and p < 0.01), HCAEC (2.0 and 20.0 microg/ml; p < 0.05 and p < 0,01), and HCMSMC (2.0 and 20.0 microg/ml; p < 0.05 and p < 0.05). The significant inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with drug concentrations more than 10 times beyond the maximal plasma level (MPL), resulting in a SI/MPL-ratio > 1. CONCLUSION: Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation.

Abciximab↗
PubMed2002

The effect of obesity on neutrophil Fc receptors and adhesion molecules (CD16, CD11b, CD62L).

BACKGROUND: There is a large body of epidemiological data associating obesity with a wide variety of clinical disease processes, including cancer and wound infections. However, defining the specific defects of neutrophils has proved difficult and often contradictory. METHODS: 27 patients having gastric bypass surgery for obesity (BMI > 40) were compared with 10 normal controls (BMI < 26). Relative neutrophil frequencies and expression of the activation antigens CD11b (integrin adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry. RESULTS: The study control group had a mean age of 37 +/- 7.6 yrs (range 30 to 57) with no significant health problems. Their mean BMI was 23 +/- 2.5 kg/m2 (range 21-26). The mean age of the sample group was 40.36 +/- 13.7 yrs (range 18 to 60) with a mean BMI of 52 +/- 8.2 kg/m2 (range 41 to 72). These patients had a large spectrum of diseases that afflict the morbidly obese, including hypertension (14), arthritis (10), exertional dyspnea (13), venous stasis (7), hypothyroidism (2), NIDDM (3), heart murmur (1), along with 8 smokers. The neutrophil frequency in the obese patients was comparable to the controls (control 49% vs obese 51%). Additionally, there was no apparent difference between obese and controls regarding CD11b or CD16 expression (424 vs 498 gmf) (267 vs 262 gmf). However, there was a significant reduction of CD62L (L-selectin) expression noted in the morbidly obese with respect to controls (102 vs 303 gmf, p < 0.001). An increased percentage of eosinophils when compared to controls (6.7% vs 1.73%, p < 0.001) was also observed. CONCLUSION: Discordant CD11b/CD62L levels, depressed levels of CD62L, and elevated eosinophil percentages support the hypothesis that a chronic inflammatory state exists in morbid obesity. Decreased levels of CD62L in the morbidly obese neutrophil pool possibly affect the neutrophil's ability to activate and migrate to sites of inflammation. This may play a role in the higher incidence of infectious complications seen in morbidly obese individuals.

Adolescent↗
PubMed1987

Functional maturation of immature B cells accumulated in the periphery by an intraperitoneal administration of a traditional Chinese medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to).

We found that an intraperitoneal (ip) injection of a traditional Chinese herbal medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to), induced accumulation of B lymphocytes (sIgM+) in the peritoneal cavity and spleen. 1) Cell surface marker analysis by a fluorescence-activated cell sorter (FACS) demonstrated that the accumulated B cells on day 4 or 7 after shosaiko-to administration (early phase) were composed mainly of sIgM+IgD- cells and suggested that these B cells maturated into sIgM+IgD+ cells on days 10 or 14 (late phase). Relative decrease of IgM+IgD+ cells at early phase was more profound in peritoneal cells (PC) than in spleen cells. 2) With respect to spleen lymphocytes, antibody responses to a thymus-independent (TI) antigen of type 2 (trinitrophenylated Ficoll) and a thymus-dependent (TD) antigen (sheep erythrocyte) were enhanced at late phase but not at early phase. In contrast, responses to trinitrophenylated lipopolysaccharide (TNP-LPS) as a TI-1 antigen and LPS as a B cell mitogen or a polyclonal B cell activator were enhanced markedly at early phase but declined at late phase. 3) With respect to peritoneal lymphocytes, responses to LPS were suppressed at early phase but recovered at late phase. Enhanced responses to TI and TD antigen at late phase in spleen lymphocytes and suppressed response to LPS at early phase in peritoneal lymphocytes may be explained by increases of IgM+IgD+ mature B cells and IgM+IgD- immature B cells, respectively, at those times. Enhanced responses to TI-1 or LPS in spleen lymphocytes at early phase may be explained by elevated sensitivity of IgM+IgD+ cells which reside in the spleen before shosaiko-to administration and receive the direct stimulation by shosaiko-to, or by acquired responsiveness of IgM+IgD- cells which migrate after stimulation with shosaiko-to.

Animals↗
PubMed2002

[Changes in hemostasis in malignant diseases].

Tumourous diseases are associated with haemorrhagic as well as thrombotic complications. The most frequent cause of haemorrhagic states in tumourous diseases is thrombocytopenic haemorrhage, consumption coagulopathy and activated fibrinolysis. Trousseau described in 1865 a mutual association between tumourous diseases and venous thromboembolism. As many as 15-20% patients with venous thromboembolism have an undetected malignity which is a prevalence of 2-3% in the population. From this ensues the relative risk of a newly diagnosed malignity which is higher during the first year after venous thromboembolism. The prevalence varies between 2% and 6%. Migrating thrombophlebitiis (saltans and migrans) are a relatively specific sign in tumours, in particular in pancreatic tumours. In the pathogenesis of venous thromboembolisms in tumourous diseases in particular the following factors play a part: elevated coagulation parameters, reduced fibrinolysis, frequent immobilization, surgical operations in the case-history, chemotherapy, hormonal therapy and central venous catheters. The authors present a brief review of changes of haemostasis in tumourous diseases, their possible diagnosis and possible pharmacological prevention and treatment of thromboembolisms.

Blood Coagulation Disorders↗
PubMed1998

ECG observations in Tibetan and Han residents of Lhasa.

In order to compare the prevalence of electrocardiographic (ECG) abnormalities suggestive of right ventricular hypertrophy in native and immigrant populations residing at high altitude, a retrospective review was undertaken of data obtained from a random survey of healthy volunteers and persons with chronic mountain sickness (CMS). All persons included in the survey were ambulatory volunteers from the general community who were evaluated at the Tibet Institute of Medical Science in Lhasa, where the elevation is 3,658 meters. The 74 residents of Lhasa, whose ECGs were studied, included 30 healthy Tibetan natives of Lhasa; 24 healthy Han (Chinese) immigrants, born at or near sea level, who had migrated to high altitude as children or adults; and 20 persons with symptoms of CMS. The ECGs of all subjects were reviewed for predetermined criteria suggestive of right ventricular hypertrophy, which were found to be present in 17% of healthy Tibetan natives, 29% of healthy Han immigrants, and 50% of CMS patients. The Han subjects who had migrated as children presented evidence of right ventricular hypertrophy more commonly than did adult immigrants. The overwhelming majority (90%) of persons with CMS were Han. Thus, the frequency of ECG abnormalities consistent with right ventricular hypertrophy was similar in healthy young Tibetan and Han men, but these abnormalities were less common in Tibetan natives than in Han who had migrated to high altitude as children or in CMS patients. The prevalence of ECG evidence of right ventricular hypertrophy increased with duration of high altitude residence among Han.

Adult↗
PubMed2001

Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein.

Long-term patency of human saphenous vein bypass grafts is low because of intimal thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to be essential for the VSMC migration that contributes to intimal thickening. We examined VSMC phenotype and MMP activity in saphenous veins obtained before and after surgical manipulation. Surgical preparation of the veins significantly increased pro-MMP-1 expression by 2-fold and significantly reduced tissue inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected. Furthermore, caseinolytic and gelatinolytic activities measured by in situ zymography were dramatically elevated by injury. The expression of desmin and smoothelin was significantly decreased by injury, whereas vimentin expression was significantly increased. In addition, these changes in phenotype and MMP activity were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our data show that surgical preparative injury induces phenotypic modulation of a subpopulation of medial VSMCs to a synthetic phenotype and increases MMP activity. This may favor matrix degradation, VSMC migration, and the subsequent intimal thickening that leads to graft failure.

Caseins↗
PubMed1999

[Arthroplasty with a mobile cup for shoulder arthrosis with irreparable rotator cuff rupture: preliminary results and cineradiographic study].

PURPOSE OF THE STUDY: Management of patients with massive irreparable rotator cuff tears associated with severe glenohumeral joint degeneration presents a difficult clinical challenge. The present study reports on 24 patients with disabling shoulder pain due to rotator cuff arthropathy treated using a bipolar arthroplasty. MATERIAL AND METHODS: Between 1995 and 1997, a bipolar shoulder arthroplasty (Biomet, Warsaw, In) was used in 24 patients (25 shoulders) with rotator cuff arthropathy. Patients were monitored for an average of 14.5 months (range 12 to 24 months). The coracoacromial ligament was maintained in all patients to provide anterosuperior stability. The rotator cuff was irreparable and no attempt was made to cover the superior defect. Postoperative results were reviewed with the Constant score and the Swanson score. In order to verify the head-shell motion and to analyze the dynamic comportement of bipolar arthroplasties, we recorded anterior active elevation and active rotations with video-fluoroscopy. RESULTS: At final the follow-up, 21 shoulders had no or slight pain. Average active flexion improved to 84.8 degrees after operation from 62.4 degrees beforehand. 13 patients achieved more than 90 degrees of active flexion after operation. Active external rotation improved from a mean 3 to 28.8 degrees. Before surgery the average Constant score was 17.62. Postoperatively, the average Constant score was 46.97 and the average Swanson score was 23.13. Complications requiring reoperation occurred in 2 cases: 1 component dislocation (Head-shell), 1 subluxation of the long head of the biceps. Radiographic evaluation at follow up demonstrated no humeral stem loosening or component migration and no bony erosion of the coracoacromial arch. Rupture of the infraspinatus tendon (absolute Constant score: p = 0.04, adjusted Constant score: p = 0.02, Swanson score: p = 0.03, Functional score: p = 0.04), preoperative anterior subluxation of the humeral head (absolute Constant score: p = 0.03, adjusted Constant score: p = 0.05, anterior elevation: p = 0.01, functional score: p = 0.04), preoperative narrowing of the acromio-humeral interval (adjusted Constant score: p = 0.02, overall mobility: p = 0.02, anterior elevation: p = 0.03) may jeopardize the subsequent success of bipolar shoulder arthroplasty. The results of this study suggest that the radius curvature of the shell must match that of the bony surface of the glenoid and the coracoacromial arch (absolute Constant score: p = 0.003, adjusted Constant score: p = 0.005, overall mobility: p = 0.002, anterior elevation: p = 0.0008, functional score: p = 0.002). Recording of anterior active elevation with video-fluoroscopy allowed to identify 3 different types of movements after bipolar shoulder arthroplasty. Recording of internal and external rotation allowed to distinguish 2 differents types of movements. Motion appeared to occur between the bipolar shell and the head. The amount of motion was variable and depended on the biomechanics. DISCUSSION AND CONCLUSION: Bipolar shoulder arthroplasty is an effective surgical option for patients with massive irreparable tears of the rotator cuff with concomitant glenohumeral arthritis. Satisfactory pain relief and modest gains in motion result in significant functional improvement in this "low functional demand" population. Predictive factors have been identified and should be discussed before surgery.

Activities of Daily Living↗
PubMed2003

Unusual physiology of scale-less carp, Gymnocypris przewalskii, in Lake Qinghai: a high altitude alkaline saline lake.

The scale-less carp (Gymnocypris przewalskii) inhabits Lake Qinghai located on the Qinghai-Tibet plateau (elevation, 3200 m) in western China. The lake waters are alkaline (pH 9.4, titratable alkalinity=30 mmol l(-1)), Mg(2+)-rich (18.7 mmol l(-1)), Ca(2+)-poor (0.30 mmol l(-1)) and saline (9 per thousand ). These fish make annual spawning migrations into freshwater rivers. We investigated the physiology of nitrogen excretion and ionoregulation of fish from the lake and river. Fish from both waters were ammonotelic, although ammonia-N excretion rates were lower in lake fish (175 vs. 344 micromol kg(-1) h(-1), P<0.05) resulting in unusually high levels of ammonia in blood plasma (2.23 vs. 0.32 mmol l(-1)), bile, liver, muscle and brain. Exposure to 0.4 mmol l(-1) total ammonia in lake water ([NH(3)]=0.16 mmol l(-1)) killed fish within 8 h. River fish survived exposure to 1.0 mmol l(-1) total ammonia in river water at pH 8.0 ([NH(3)]=0.023 mmol l(-1)) for 24 h suggesting high ammonia tolerance in lake fish. High glutamate dehydrogenase and glutamine synthetase activities in tissues probably allow the fish to alleviate ammonia toxicity by amino acid accumulation. Neither lake nor river fish relied on urea excretion to remove excess N. Urea-N excretion rates were below 20 micromol kg(-1) h(-1) for both groups, and levels of urea in plasma and tissues were moderate. When exposed to elevated ammonia, urea-N excretion increased slightly (approximately 50 micromol kg(-1) h(-1)) and liver and muscle urea levels increased in the river fish. Plasma ion levels were within the range typical of cyprinids, but river fish had significantly higher plasma [Na(+)] and [Cl(-)] and lower [K(+)] than fish from the lake. During 48-h lake-to-river water transfer, plasma Na(+) and Cl(-) levels rose significantly. Significantly higher Na(+)/K(+)-ATPase activity in the gills of river fish may be related to the higher plasma ion levels. Plasma [Mg(2+)] and [Ca(2+)] were tightly regulated despite the great differences in the lake and river water levels.

Alkalies↗
PubMed1997

Soluble CD44 splice variants in metastasizing human breast cancer.

The local expression of CD44 splice variants in human breast cancer tissue has been previously shown to be associated with metastasis. We show here that elevated systemic serum levels of CD44 splice variants occur in breast cancer and may represent a new tool for staging and differential diagnosis. Sera of node-negative and node-positive breast cancer patients in comparison with healthy control subjects were analyzed for serum CD44 (sCD44) and 2 different splice variants (v5 and v6). Node-positive breast cancer patients showed significantly (p < 0.01) elevated levels of sCD44-v5 and -v6 splice variants in comparison to node-negative patients and healthy controls. None of the node-negative breast cancer patients or healthy controls showed elevated levels of both sCD44-v5 and -v6. Interestingly, no differences were seen for serum levels of non-spliced sCD44-standard between the 3 groups. Soluble forms of CD44 variants may promote migration of tumor cells. This may occur through interference with tumor cell adhesion or by modulation of immune defense mechanisms.

Alternative Splicing↗
PubMed2002

Astrocyte delivery of glial cell line-derived neurotrophic factor in a mouse model of Parkinson's disease.

Primary astrocytes were genetically modified ex vivo to express recombinant glial cell line-derived neurotrophic factor (GDNF) and subsequently were tested for their ability to provide neuroprotection to dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease. A replication-defective retrovirus was constructed, which contained the rat GDNF sequence and a sequence encoding a beta-galactosidase (beta-gal)/neomycin phosphotransferase fusion protein, linked via an internal ribosomal entry site. Murine astrocytes transduced with this vector secreted GDNF into the culture media at the rate of 115 +/- 34 pg/24 h/10(5) cells and expressed cytoplasmic beta-gal, whereas control nontransduced astrocytes were negative for GDNF production and cytoplasmic beta-gal expression. Mice that received implants of GDNF-producing astrocytes into the striatum or nigra displayed elevated levels of GDNF compared to mice that received control nontransduced astrocytes. In addition, tissue content of GDNF was increased bilaterally and in brain regions both proximal and distal to the graft, even though astrocyte migration away from the graft site did not occur. Importantly, GDNF-producing astrocytes provided marked neuroprotection of nigral dopaminergic perikarya, and partial protection of striatal dopaminergic fibers, when implanted into the midbrain 6 days prior to a retrograde 6-OHDA lesion, as assessed by tyrosine hydroxylase immunohistochemistry. Similarly, GDNF-producing astrocytes prevented the acquisition of amphetamine-induced rotational behavior in 6-OHDA-treated mice and completely prevented dopamine depletion within the substantia nigra, as assessed by high-performance liquid chromatography. These results indicate that continuous exposure to low levels of GDNF provided by transgenic astrocytes provides marked neuroprotection of nigral dopaminergic neurons. (c)2002 Elsevier Science (USA).

Amphetamines↗
PubMed2002

The effect of dehydroepiandrosterone on hemorrhage-induced suppression of cellular immune function.

OBJECTIVE: To determine whether the steroid hormone dehydroepiandrosterone (DHEA) improves cellular immune functions after hemorrhagic shock. DESIGN AND SETTING: Prospective controlled study in a research laboratory at an university medical center. SUBJECTS: Male NMRI mice. INTERVENTIONS: Animals received 0.9% saline or DHEA (20 mg/kg subcutaneously) before induction of a volume-controlled hemorrhagic shock (55% of estimated circulating blood volume) by retro-orbital puncture. One hour after hemorrhage mice underwent fluid resuscitation by intravenous infusion of lactated Ringer's solution (300% of the shed blood). Separate groups of mice were killed to obtain whole blood and spleen 1 h after hemorrhage, 1 h after fluid resuscitation, and 24 h after hemorrhage to determine lymphocyte distribution (CD4(+), CD8(+), NK1.1-AG(+)), splenocyte apoptosis, and plasma concentrations of tumor necrosis factor-alpha and interleukin-10. MEASUREMENTS AND RESULTS: Hemorrhage in control mice was associated with a rapid increase in circulating NK cell numbers. Elevated splenocyte apoptosis, an increased CD4/CD8 ratio, and decreased number of circulating CD8(+) T-cells was observed 24 h after hemorrhagic shock. DHEA administration was accompanied by a normalization of splenocyte apoptosis and lymphocyte migration. Induction of hemorrhagic shock did not affect TNF-alpha or IL-10 plasma concentrations in either treatment group. CONCLUSIONS: DHEA administration improves cellular immune function after hemorrhage and may therefore be beneficial in patients with hemorrhagic shock.

Animals↗