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J Brain

Publications and source records attributed to J Brain.

11 recordsLinked to original sources
PubMed2001

Suppressed apoptosis of pre-B cells in bone marrow of pre-leukemic p190bcr/abl transgenic mice.

Mice transgenic for a p190bcr/abl construct develop pre-B cell leukemia/lymphoma, providing a model of Ph+ ALL. To investigate events in tumorigenesis, immunofluorescence labeling, flow cytometry and a short-term culture assay were used to quantitate precursor B cells and their apoptotic rates in bone marrow of p190bcr/abl transgenic mice over a wide age range. Malignancies appeared rapidly at 8-12 weeks of age, followed by slower tumor onset. At 8-12 weeks in normal mice, the apoptotic rate fell among pro-B cells but increased steeply among pre-B cells, while the total number of B lineage cells declined. In contrast, in p190bcr/abl transgenic mice over the same time period, while pro-B cells remained normal in apoptotic rate and number, apoptosis of pre-B cells was markedly inhibited and the number of B lymphocytes increased. At later ages (14-30 weeks), B cell precursors in control mice remained constant in apoptotic activity and number, while in the few surviving transgenic mice B cell populations were expanded. The results reveal characteristic changes in apoptotic activity among B cell precursors in bone marrow during early life, severely perturbed in preleukemic p190bcr/abl transgenic mice by a preferential suppression of pre-B cell apoptosis. p190bcr/abl may thus promote leukemogenesis by permitting aberrant cells generated during early B cell development to evade a normal quality checkpoint and negative selection.

Age Factors↗
PubMed1999

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Administration, Inhalation↗
PubMed1994

Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction.

We determined the effect of a graded increase in lung exposure to a toxic smoke by increasing smoke tidal volume (VT) or the number of smoke breaths. Sheep were anesthetized and then insufflated with cooled cotton toweling smoke; VT was 5, 10, or 20 ml/kg, and smoke breaths were varied from 12 to 48. The smoke had a uniform particle size (3 +/- 0.4 microns diam). Peak carboxyhemoglobin levels varied from 8 +/- 2 to 45 +/- 4% in the lowest to highest exposure groups, respectively. Animals were monitored unanesthetized for 24 h, and then they were killed. Oxygenation (ratio of arterial PO2 to fraction of inspire O2) decreased from 480 +/- 21 to 200 Torr, and compliance decreased by approximately 50% in the highest smoke exposure groups, whereas only a modest decrease in oxygenation and no compliance changes were seen with lesser exposures. A moderate tracheobronchitis, some atelectasis, and no alveolar edema were noted in the lower smoke exposure groups, whereas severe tracheobronchitis, airway edema, and alveolar atelectasis were observed in the highest exposure group. Only modest alveolar flooding was noted. Impaired oxygenation and anatomic injury correlated best with the total smoke delivered (r = 0.59). Increasing VT from 5 to 20 ml/kg did not increase airway or alveolar injury if the total smoke mass delivered was maintained constant. The degree of impaired oxygenation did not correlate with measured lung water (r = 0.27) or lung lymph flow (r = 0.31).

Aerosols↗
PubMed1994

Smoke inhalation injury in sheep is caused by the particle phase, not the gas phase.

The inhalation of smoke can produce severe lung injury, particularly to airways. We assessed the role of the toxic compounds in the particle phase vs. those in the gas phase of smoke in the injury process by filtering out all particles > 0.3 micron diam before exposure. Adult sheep (n = 16) were insufflated with a well-characterized cellulose smoke. Mean particle size was 3 +/- 0.4 micron diam. A standardized dose of 12 breaths of whole or filtered smoke (n = 8/group) was given to sheep under anesthesia with a tidal volume of 20 ml/kg. Sheep were awakened and monitored for 24 h and then killed. Peak carboxyhemoglobin levels were 40-45% in both groups. Severe respiratory failure occurred only in the whole-smoke group, as evidenced by an increase in shunt fraction from a control of 0.04 +/- 0.02 to 0.28 +/- 0.05, a decrease in lung compliance of 50%, and histological evidence of severe airway mucosal edema, ulceration, and bronchorrhea. No significant physiological, histological, or biochemical changes were noted in the filtered-smoke group.

Animals↗
PubMed1992

New kappa-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus.

The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]-2- [(alkylamino)methyl]piperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]- 2-[[1-(3-oxopyrrolidinyl)]methyl]piperidine (10) possesses high activity in the rabbit vas deferens (LVD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antinociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg, sc). The spirocyclic analogue 8-[(3,4-dichlorophenyl)acetyl]-7-(1-pyrrolidinylmethyl)-1,4-dio xa-8- azaspirol4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

Analgesics↗
PubMed1981

Rectal membrane: an unusual complication following use of the circular stapling instrument for colorectal anastomosis.

This is the first report of a rectal membrane forming at the site of a low end-to-end rectal anastomosis performed with the EEA circular gun. The diagnosis was made by Gastrografin enema that revealed disparity between the staple line diameter and the bowel lumen. The condition was treated easily by digital breakage of the membrane; there was a complete cure. A brief discussion of the etiology of anastomotic strictures and other gastrointestinal membranes follows.

Adenocarcinoma↗
PubMed1977

Child's play.

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Child↗