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PubMed1976

Macrophage migration inhibition factor activity in the aqueous humor during experimental corneal xenograft and allograft rejection.

Macrophage migration inhibition factor (MIF), a soluble mediator of delayed hypersensitivity, was assayed for in the aqueous humor of rabbits undergoing corneal graft rejection. Penetrating and interlamellar xenografts and interlamellar allografts were performed in rabbits, and aqueous humor early in the course of xenograft and allograft rejection, and MIF activity was present during the course of the active rejection. This activity returned to near normal after the active rejection resolved. No significant MIF activity could be measured during the nonspecific inflammations produced by alkali burns, multiple paracenteses, intracorneal clove oil, mechanical debriding of the endothelium.

Animals↗
PubMed1994

Cell cycle kinetics in rat prostatic epithelia: nuclear migration during G2 phase.

Proliferative events in luminal epithelial cells of the rat ventral prostate were studied in 2 experiments. In experiment 1 a longitudinal survey of the rat prostate was conducted between 22 and 88 days of age. The pattern of temporal changes in the weight of the ventral prostate paralleled that of the testis, an observation consistent with the knowledge that the prostate is an androgen target organ. However, the total number of mitotic cells per prostate showed a biphasic pattern of distribution. The count was high (82 per prostate) in the prostate of 22-day-old rats and it decreased to a low value (25 per prostate) by age 30 days, a period corresponding to the onset of puberty in rats. The total mitotic count per prostate increased gradually and reached a peak (85 per prostate) around age 60 days when it started to decline gradually despite a continuous increase in prostatic weight. In experiment 2 cell cycle parameters of these cells were determined in young adult rats (age 70 days or 250 gm. body weight) by an in vivo 3H-thymidine pulse-chase approach. The apparent duration of various phases of the cell cycle was estimated as G1--11.5 hours, S--6.5 hours, G2--3.0 hours, M--2.0 hours and total cell cycle--23 hours. The fraction of cells in the S phase was 2.1%, which was extrapolated to give rise to a total growth fraction of 7.4%. In addition, it was noted that there was a migration of the nucleus from the base toward the apex of the epithelial cells during the G2 phase of the cell cycle in preparation for cell mitosis. Following mitosis nuclei of the 2 daughter cells returned to the usual basal position. These parameters will be used as basis of our future kinetic studies in the rat prostate.

Animals↗
PubMed1987

C5a-specific modulation of phagocyte functions in patients with localized bacterial infections.

Chemotaxis, enzyme release and superoxide-anion (O2-) generation of purified peripheral blood neutrophils (PMN) and monocytes were studied in a total of 87 patients suffering from localized bacterial infections. Shortly after disease onset, single or several PMN functions became non-responsive to the complement split product C5a. Functional activities elicited by the synthetic peptide f-met-leu-phe or leukotriene B4 remained unaltered. C5a-specific impairment lasted one to several days and returned to normal with the subsidence of the disease. C5a elicited release of beta-glucuronidase as well as generation of superoxide-anions was seen more often to be impaired as compared to chemotactic migration. In contrast to PMN, monocytes from the same patients failed to show paralleling C5a-specific functional alterations. There was no correlation between impairment of PMN functions and plasma levels of the complement split-products C3a and C4a as determined by RIA. It is concluded that in acute infectious disease a graded C5a-specific modulation of PMN functions may be present. This phenomenon is transient and not paralleled by functional alterations of monocytes or changes in plasma complement levels.

Bacterial Infections↗
PubMed1999

Role of abdominal drains in perforated duodenal ulcer patients: a prospective controlled study.

BACKGROUND: Duodenal ulcer perforation is a common emergency in south India, with about 100-120 cases being treated at Jawaharalal Institute of Post Graduate Medical Education and Research each year. The routine to date has been to leave two tube drains: one in the Morrison's pouch and one in the pelvis after omental patch closure. This study was conducted to test the efficacy and safety of drain usage routinely after duodenal ulcer perforation closure with Roscoe Graham omental patch technique. METHODS: In this prospective controlled study, 44 patients formed the test group (without drains) and 75 patients formed the control group (with abdominal drainage). Only patients of perforated duodenal ulcer closed with Roscoe Graham omental patch technique were included in the study. The incidence of postoperative fever, wound infection, time for return of bowel function and duration of hospital stay were noted. Details of drainage noted were the mean amount of daily drainage, mean time of drain removal and occurrence of drain-related complications. Peritoneal fluid, wound discharges, drain tips and drain wounds were cultured. Abdominal ultrasound was performed in all patients in the second postoperative week or if earlier indicated to detect intra-abdominal collections. RESULTS: It was found that there was no difference in incidence or duration of postoperative pyrexia, return of bowel function or postoperative hospital stay between the two groups. Routine use of drains was not effective in preventing postoperative fluid collection nor in decreasing the incidence of intra-abdominal abscesses. The migration of bacteria from the exterior to the peritoneal cavity via the drain was also demonstrated. Drains were found to cause morbidity including intestinal obstruction. CONCLUSION: The routine use of drains was found to be neither safe nor effective in patients of perforated duodenal ulcer treated by omental patch closure.

Adult↗
PubMed1982

Altered factor VIII in acute respiratory failure.

Acute respiratory failure is characterized by pulmonary vascular injury and increased endothelial permeability. Since endothelial cells synthesize or release factor VIII, we studied factor VIII:antigen, factor VIII:von Willebrand's factor, and factor VIII:coagulant activity in 100 patients with acute respiratory failure, in 29 critically ill patients without evidence of lung disease, and in 60 normal subjects. As a group, patients with respiratory failure had factor VIII:antigen levels that were five times normal, whereas their factor VIII:coagulant and von Willebrand's activities were normal or above normal. However, there was a remarkable disproportion between the levels of factor VIII:antigen and those of factor VIII:coagulant and von Willebrand's factor. In the other ill patients and in the normal group, these levels were in close proportion. In patients with respiratory failure, both slowly and rapidly migrating components of factor VIII:antigen had abnormal electrophoretic patterns; in moderate and severe cases, there was a marked increase in the fast component. Patients who recovered from acute respiratory failure had electrophoretic patterns that returned toward normal. Factor VIII:antigen may be a sensitive circulating indicator of pulmonary endothelial injury and repair.

Acute Disease↗
PubMed2003

Nature, frequency, and predictors of secondary procedures after endovascular repair of abdominal aortic aneurysm.

OBJECTIVES: Endovascular stent grafting offers a potentially less invasive option for treatment of abdominal aortic aneurysm. Clinical benefit has been demonstrated with respect to early parameters such as blood transfusion, return of gastrointestinal function, and length of hospital stay. Endovascular repair, however, has been criticized on the basis of inferior long-term outcome. Secondary procedures may be necessary to address durability issues such as migration, high-pressure endoleak, graft limb thrombosis, and degeneration of the stent-fabric structure itself, issues that may compromise the primary goal of aneurysm repair, protection from rupture. METHODS: Between 1996 and 2002, 703 patients underwent endovascular treatment of infrarenal abdominal aortic aneurysm at The Cleveland Clinic Foundation. During this time, five devices were used: Ancure, AneuRx, Excluder, Talent, and Zenith. Outcome was assessed with physical examination, lower extremity arterial studies, plain abdominal radiography, and computed tomography at discharge, at 1, 6, and 12 months postoperatively, and annually thereafter. Secondary procedures were defined as any procedure, exclusive of diagnostic angiography, performed after stent graft implantation, directed at treatment of aneurysm-related events. Multivariable statistical techniques for censored data (Cox proportional hazards modeling) were used to determine baseline parameters associated with need for secondary procedures over follow-up, with calculation of hazards ratio (HR) and 95% confidence interval (CI). RESULTS: Patient follow-up averaged 12.2 +/- 11.7 months. Patient survival was 90% +/- 1.4% at 1 year, 78% +/- 2.6% at 2 years, and 70% +/- 3.8% at 3 years. Aneurysm rupture occurred in 3 patients (0.4%), accounting for rupture risk of 1.4% over the first 2 years of follow-up (Kaplan-Meier method). Overall, 128 secondary procedures were required in 104 patients (15%), with a cumulative risk of 12% +/- 1.5% at 1 year, 24% +/- 2.8% at 2 years, and 35% +/- 4.4% at 3 years after stent graft implantation. Among the secondary procedures, new stent grafts and extensions were placed in 34 patients (27%), embolization of endoleak was performed in 33 patients (26%), and open surgical conversion was undertaken in 11 patients (9%). Periprocedural mortality of secondary procedures was 8% overall, but was 18% for patients undergoing open surgical conversion. Multivariable modeling identified the date the procedure was performed (HR, 1.53 per 3-month period of study; CI, 1.22-1.92; P <.001) and aneurysm size (HR, 1.35 per centimeter of minor axis; CI, 1.13-1.60; P <.001) as independent predictors of need for secondary procedures. CONCLUSIONS: Current endovascular devices are associated with a relatively high rate of complications over mid-term follow-up, culminating in frequent need for secondary remedial procedures. With strict follow-up imaging compliance, however, risk for rupture and aneurysm-related death remain exceedingly low. Newer technology may achieve improved durability and a lower requirement for secondary procedures, while maintaining the minimally invasive nature of presently available devices.

Aged↗
PubMed2005

Long-term results after anterior cervical discectomy and fusion with allograft and plating: a 5- to 11-year radiologic and clinical follow-up study.

STUDY DESIGN: A retrospective review. OBJECTIVES: To determine the clinical and radiologic outcomes beyond 5 years after anterior cervical discectomy and fusion with allograft and plating. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion is commonly performed for cervical disc disease. The routine use of allografts and plating, though increasing in popularity, has not been well studied for long-term results and complications. METHODS: Seventy-one patients who had anterior cervical discectomy and fusion with allograft and plating an average of 7.2 years prior responded to an invitation to return for a follow-up clinical and radiographic review. RESULTS: At final review, symptom resolution remained greater than 82% and fusion occurred in 92.6% of the disc spaces operated on. No graft extrusion or migration occurred. Based on our strict criteria, the rates of collapse and subsidence were high, at 47.9% (34 patients) overall. However, in only 6 patients (8.5%) did segmental kyphosis result, none of whom required any revision surgery in the follow-up period. Implant complications occurred in 7 patients (9.9%), none of whom required revision surgeries. Adjacent level degeneration occurred in 52 patients (73.2%). Further cervical spine surgeries were required in 14 patients (19.7%), 2 for inadequate decompression, and 12 for adjacent level disease. Segmental and global cervical lordosis was restored and maintained by the surgery over the study period. CONCLUSIONS: The use of allografts and plate fixation in combination for anterior cervical discectomy and fusion does not compromise the radiologic and clinical outcomes while providing the advantages of donor site morbidity elimination, restoration of cervical segmental lordosis, and not requiring postoperative immobilization.

Adult↗
PubMed2003

[Effect of long-term fertilization practices on mobility of phosphorus in a Huangnitu paddy soil receiving low P input in the Taihu Lake region, Jiangsu Province].

Analysis of mobile forms of phosphorus of a Huangnitu, a typical paddy soil in the Taihu Lake region, Jiangsu was conducted. The soil has been put into a scheme of longterm fertilization treatments for 13 years. Total P content varied in arrange of 0.3-0.5 g.kg-1 under a range of total P fertilizer input of 0-53 kg/(hm2.a). As estimated from the total P pool values by mass balance principle, the soil had been subjected to water loss of P 2-8 kg/(hm2.a), with that under chemical fertilizers only being the biggest. The ratio of soluble P to the total was in a range of 0.2%-0.4%, without significant influence by the different fertilization schemes. While chemical fertilizer plus pig slurry manure applications had remarkably enhanced the resin-P pool by 20-40 mg.kg-1, P mobilization was not observed due to combined application of chemical fertilizers and straw amendments despite of the increase of the SOM. Therefore, P water loss in paddy soils might have active under continuous chemical fertilization alone in agriculture of this region and could not be accounted for by dissolution in water and subsequent runoff migration. For reducing the present prominent non point source pollution of N and P in the region, it is suggested that chemical fertilizers are applied in combination with an appropriate amount of manure or straw return for reducing soil P loss and, in turn, the non-point source pollution loading.

Crops, Agricultural↗
PubMed1991

Use of determinations of 7-lathosterol (5 alpha-cholest-7-en-3 beta-ol) and other cholesterol precursors in serum in the study and treatment of disturbances of sterol metabolism, particularly cerebrotendinous xanthomatosis.

The sterol composition of sera from patients with cerebrotendinous xanthomatosis (CTX) was investigated by gas chromatographic analysis of saponified extracts, using a polar (CP Wax 52CB) and an apolar (CP Sil 5CB) capillary column. Apart from already known sterols, the presence of increased amounts of 8-lathosterol (5 alpha-cholest-8(9)-en-3 beta-ol) and significant amounts of 8-dehydrocholesterol (cholesta-5,8-dien-3 beta-ol) were noticed. The latter compound has not been detected previously in human serum and possibly represents a hitherto unknown cholesterol precursor. The apparently elevated levels of delta 8-sterols in CTX serum suggests partial inhibition of migration of the 8,9 double bond to the 7,8 position in this condition. The concentration of 7-lathosterol, an indicator of cholesterol production rate, is also highly elevated in CTX serum and quickly returns to normal values after oral bile acid therapy. Determinations of serum lathosterol are not only useful in the follow-up of therapy of CTX patients, but also in the follow-up of hypercholesterolemic patients treated with either HMG-CoA reductase inhibitors or bile acid sequestrants.

Adult↗
PubMed1981

[Atrial stimulation and intranodal migration of sinus pacemaker in man (author's transl)].

In order to demonstrate, in man, sinus node pacemaker shift following atrial stimulation, we compared, in 26 patients, the curve of sinus node function obtained with Strauss' method with that resulting by the scanning with premature atrial stimulation of the first returning cycle following either a single premature atrial induced beat (140 ms shorter than the basic cycle) (group A), or a train of 8 consecutive atrial beats induced with a rate slightly faster (10 beats/m) than the control sinus rhythm (group B). Assuming that no changes in sinus pacemaker automaticity or in sinoatrial conduction occur owing to atrial stimulation, curves with the same shape should be observed if the site of the dominant pacemaker remains unchanged: whereas, different lengths of the compensatory phase (zone I) should be expected if an intranodal pacemaker shift occurs. For evaluating the length of the compensatory zone (zone I), we calculate, on the curve of the sinus node function, the mean value of the relation points included in the first third of the reset zone (zone II). According to our results, the length of the compensatory phase (zone I) evaluated on the curve resulting by the scanning of the first returning cycle following either a single premature atrial induced beat (group A), or eight consecutive atrial beats (group B) was shorter than that observed with the original Strauss' method (10% and 18% respectively). However, only in the group B, this difference was statistically significant. In addition, a significant inverse relationship between the shortening of the compensatory zone and the sinoatrial conduction index was also observed. Considering that our results have been corrected in such way as to repeal eventual changes in sinus pacemaker automaticity or sinoatrial conduction following atrial stimulation, the shortening of the compensatory zone, we have observed in our patients, strongly suggests an intranodal sinus pacemaker shift. If we assume that this result could represent an indirect evidence of this phenomenon, some clinical implications may follow: 1) another limitation, in addition to others known (intraatrial conduction delay, sinus arrhythmia, changes in sinus node automaticity, difference between retrograde and antegrade conduction time) could decrease the accuracy of atrial stimulation techniques in the estimation of the sinoatrial conduction time; 2) sinus pacemaker shift following atrial stimulation, may induce an understimulation of the true sinoatrial conduction time; however, according to our results, the error is generally small, so that it does no preclude the usefulness of atrial stimulation techniques in the evaluation of sinoatrial conduction; 3) the more evident and significant shortenings of the compensatory phase occurred with atrial pacing technique: this finding could explain why shorter sinoatrial conduction times are generally observed with Narula's method in comparison with Strauss' method.

Adult↗
PubMed1993

Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes.

The molecular mechanisms by which overloaded cardiac myocytes increase the cell size (hypertrophy) remain unknown. We have previously shown that mechanical loading increased the protein synthesis and the expression of proto-oncogene c-fos mRNA (Komuro, I., Kaida, T., Shibazaki, Y., Kurabayashi, M., Katoh, Y. Hoh, E., Takaku, F., and Yazaki, Y. (1990) J. Biol. Chem. 265, 3595-3598; Komuro, I., Katoh, Y., Kaida, T., Shibazaki, Y., Kurabayashi, M., Hoh, E., Takaku, F., and Yazaki, Y. (1991) J. Biol. Chem. 266, 1265-1268). It has been known that both mitogen-activated protein (MAP) kinase and S6 kinase can be activated by many kinds of growth factors. To clarify whether MAP kinase(s) and S6 kinase(s) are associated with the intracellular signaling of cardiac hypertrophy induced by mechanical loading, we cultured neonatal rat cardiac myocytes in deformable dishes and imposed an in vitro mechanical loading by stretching the adherent myocytes. In this study, we demonstrated that 1) myocyte stretching maximally activated a kinase activity toward myelin basic protein (MBP) at 10 min after stretching, and the kinase activity returned to the control level at 30 min after stretching; 2) kinase assays in MBP-containing gel, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed that stretch-induced MBP kinase activity mainly migrated at 42 kDa in the immunoprecipitated fraction of anti-MAP kinase antibody, suggesting that the stretching mainly increased the 42-kDa MAP kinase activity in cardiac myocytes; 3) phosphorylation of MAP kinase was induced after stretching cardiac myocytes; 4) when protein kinase C was depleted by preincubating myocytes with 100 nM 12-O-tetradecanoyl-phorbol-13-acetate for 24 h or 2 nM staurosporine for 30 min, stretch-induced MBP kinase activity was decreased by approximately 60-70% as compared with the kinase activity in myocytes without protein kinase C depletion; 5) although the receptor tyrosine kinases were depleted by preincubating myocytes with 50 microM tyrphostin or 20 microM genistein for 30 min, there was no change in the stretch-induced MBP kinase activity; 6) stretch-induced MBP kinase activity was partially dependent on transsarcolemmal influx of Ca2+; 7) myocyte stretching also increased S6 peptide (RRLSSLRA) kinase activity in the anti-S6 kinase II antibody immunoprecipitates. From these results, we conclude that myocyte stretching increases the activities of MAP kinase and S6 peptide kinase, which may play an important role in the induction of the specific genes and the increase in the protein synthesis.

Alkaloids↗
PubMed1987

Labor migration in Southern Africa and agricultural development: some lessons from Lesotho.

The authors examine policy issues with regard to attempts by Lesotho to develop agriculture as a viable alternative to out-migration for employment and income. They argue that "an appropriate agricultural development strategy for Lesotho would emphasize relatively labor- and land-intensive agricultural enterprises, such as horticultural operations and closely managed livestock activities. The suggestion is that only agriculture of this kind will generate sufficient returns on a limited land base to dissuade men from going to the mines. Our paper develops a more complete theoretical and empirical foundation for examining this as well as other agricultural strategies."

Africa↗
PubMed1997

Pre-mitotic nuclear migration in subsidiary mother cells of Tradescantia occurs in G1 of the cell cycle and requires F-actin.

We have studied pre-mitotic nuclear migration in living subsidiary mother cells (SMCs) of Tradescantia virginiana. Divisions in the four SMCs of each stomatal complex are asymmetrical and are preceded by the migration of nuclei from random locations in the cells to positions adjacent to the central guard mother cells (GMCs). In newly polarised SMCs, nuclei display erratic movements which gradually dampen over time. In older complexes, where nuclear migration occurred earlier in the ontogeny of the leaf, nuclei are stably positioned and change in morphology from spherical to dome-shaped. Labelling with bromodeoxyuridine (BrdU) shows that SMCs polarised in G1 of the cell cycle and remain polarised for a minimum of 22 h before entering mitosis, while the inducing GMCs stay in G1. Centrifugation (1,320 g, 15 min) of epidermal peels displaces the majority of nuclei to the centrifugal end of cells, including nuclei in polarised SMCs. After centrifugation, most SMC nuclei return towards the GMCs within 100 min in control and 5 microM oryzalin treated peels. However, nuclei are unable to reposition in the presence of cytochalasin B (5 micrograms/ml). Thus, the signal for SMC polarisation is issued very early in the ontogeny of the cells (G1), is apparently sustained for a prolonged period, and results in the actin-dependent migration of nuclei towards the GMC. Cytological changes and nuclear migrations similar to those occurring in polarising SMCs can be induced by a local application of pressure to the surface of epidermal cells.

Actins↗
PubMed1990

[The brain drain, internal migration, and management of human resources in China].

"A major impediment to Third World development, the brain drain in the People's Republic of China originates from a variety of factors which, to a notable extent, differ from more traditional causes identified in most other developing countries. In addition to political management of human resources, the organization itself of the educational system and the regularisation of internal migration are basic causes of China's massive brain emigration. Through various relations maintained by the Chinese Government with its expatriate communities, and in order to promote (and finance) the economic and technological process engaged in the early 1980s, a number of measures and incentives to integrate more rationally the resident professionals and to promote the return of expatriate brains have been adopted.... Uncertainties today impede any clear assessment of the...viability of China's official policy of recognition and integration of national professionals." (SUMMARY IN ENG)

Asia↗
PubMed2001

Is the detection of the first arrival date of migrating birds influenced by population size? A case study of the red-backed shrike Lanius collurio.

Many analyses do not consider the problems associated with the effects of population size on encounter recording. Population size could impact on the detection of bird arrival time as there is a higher probability of observing earlier arrival when the population size is greater and the song activity of birds is increased, as occurs with a larger population. As a case study, we have analysed data on the red-backed shrike Lanius collurio collected in Western Poland during 1983-2000. In this period the red-backed shrike's return to its breeding sites became significantly earlier whilst the contemporary population size increased significantly. To eliminate linear trends through time we have worked on the standardised residuals from regression of both arrival time and population size on year. The correlation between arrival time and population size residuals was significantly negative, further supporting the link between detection and population size. This finding suggests that, in studies of avian migration and its changes over time, the relationship between arrival date and population size needs to be considered.

Animals↗
PubMed2004

Monarch butterfly spatially discrete advection model.

We study the population cycles of the Monarch butterfly using one of the simplest systems incorporating both migration and local dynamics. The annual migration of the Monarch involves four generations. Members of Generations 1-3 (occasionally 4) migrate from the over-wintering site in Central Mexico to breeding grounds that extend as far north as the Northern United States and Southern Canada. A portion of the Generation 3 and all members of the Generation 4 butterflies begin their return to the over-wintering grounds in August through October where they enter reproductive diapause for several months. We developed a simple discrete-time island chain model in which different fecundity functions are used to model the reproductive strategies of each generation. The fecundity functions are selected from broad classes of functions that capture the effects of either contest or scramble intraspecific competition in the Monarch population. The objectives of our research are multiple and include the study of the generationally dependent intraspecific competition and its effect on the pool size of migrants as well as the persistence of the overall butterfly populations. The stage structure used in modeling the Monarch butterfly dynamics and their generationally dependent reproductive strategies naturally support fluctuating patterns and multiple attractors. The implications of these fluctuations and attractors on the long-term survival of the Monarch butterfly population are explored.

Animal Migration↗
PubMed2003

The 'Abtropfung phenomenon' revisited: Dermal nevus cells from congenital nevi cannot activate matrix metalloproteinase 2 (MMP-2).

Since Unna's Abtropfung hypothesis, the process of migration of nevus cells in the dermis remains unknown. To investigate its mechanisms, we studied the role of gelatinases in dermal nevus cells obtained from congenital pigmented nevi, which are major actors in the remodeling of basement membrane proteins. Our previous studies have shown that dermal nevus cells express pro-matrix metalloproteinase (MMP)-2 exclusively and cannot return to the dermis when seeded together with keratinocytes on top of the dermis in a skin reconstruction model. To examine why MMP-2 was not in its active form, we used Western blot to study the expression of members of the MMP-2 activation pathway (membrane type 1-MMP and tissue inhibitor of metalloproteinase-2), which proved to be normally expressed. To induce the dermal passage of nevus cells artificially, we also tried to activate gelatinases with phorbol-12-myristate-13-acetate and epidermal growth factor, using epidermis reconstructed with nevus cells. No migration in the dermis could be triggered. We conclude that the absence of active MMP-2 is due to a functional blockade of its activation pathway and may prevent dermal nevus cells from reaching the dermal compartment in skin reconstructs. Furthermore, our findings reinforce the concept that dermal nevus cells originating from congenital nevi are in a quiescent status.

Adolescent↗
PubMed2000

A cell-survival factor (N-acetyl-L-cysteine) alters the in vivo fate of constitutively proliferating subependymal cells in the adult forebrain.

The adult mouse brain contains a population of constitutively proliferating subependymal cells that surround the lateral ventricle and are the direct progeny of the neural stem cell. Constitutively proliferating cells divide rapidly; 6 days after labeling, 60% of their progeny undergo cell death, 25% migrate to the olfactory bulbs, and 15% continue to proliferate within the subependyma. We have intraventricularly infused a cell survival factor N-acetyl-L-cysteine (NAC), which is known to have survival effects without concomitant proliferative effects on cells in vitro, and examined the resulting fate of cells spared from the normally occurring cell death. NAC infusion for 5 days results in a five-fold increase in the number of retrovirally labeled subependymal cells compared to saline-infused controls. The increase in the number of subependymal cells is directly proportional to the amount of time during which NAC is present and is not due to increased proliferation. While NAC is able to keep all the normally dying progeny alive, the cells spared from death remain confined to the subependyma lining the lateral ventricles and do not migrate to the olfactory bulbs (one normal fate of constitutively proliferating progeny) or into the surrounding brain parenchyma. When animals survive for an additional 6 days following NAC infusion, the number of retrovirally labeled subependymal cells returns to control values, indicating that the continued presence of NAC is necessary for cell survival. These data suggest that preventing cell death is not sufficient to keep all of the progeny of these cells in a proliferative mode.

Acetylcysteine↗