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J Dickstein

Publications and source records attributed to J Dickstein.

7 recordsLinked to original sources
PubMed2000

Tracheal constrictor drive above the apneic threshold in anesthetized dogs.

We have previously shown that raising arterial PCO(2) (Pa(CO(2))) by small increments in dogs ventilated below the apneic threshold (AT) results in almost complete tracheal constriction before the return of phrenic activity (Dickstein JA, Greenberg A, Kruger J, Robicsek A, Silverman J, Sommer L, Sommer D, Volgyesi G, Iscoe S, and Fisher JA. J Appl Physiol 81: 1844-1849, 1996). We hypothesized that, if increasing chemical drive above the AT mediates increasing constrictor drive to tracheal smooth muscle, then pulmonary slowly adapting receptor input should elicit more tracheal dilation below the AT than above. In six methohexital sodium-anesthetized, paralyzed, and ventilated dogs, we measured changes in tracheal diameter in response to step increases in tidal volume (VT) or respiratory frequency (f) below and above the AT at constant Pa(CO(2)) ( approximately 40 and 67 Torr, respectively). Increases in VT (400-1,200 ml) caused significantly more (P = 0.005) tracheal dilation below than above AT (7.0 +/- 2.2 vs. 2.8 +/- 1.0 mm, respectively). In contrast, increases in f (14-22 breaths/min) caused similar (P = 0.93) tracheal dilations below and above (1.0 +/- 1.3 and 1.0 +/- 0.8 mm, respectively) AT. The greater effectiveness of dilator stimuli below compared with above the AT is consistent with the hypothesis that drive to tracheal smooth muscle increases even after attainment of maximal constriction. Our results emphasize the importance of controlling PCO(2) with respect to the AT when tracheal smooth muscle tone is experimentally altered.

Animals↗
PubMed1999

The traffic of resting lymphocytes through delayed hypersensitivity and chronic inflammatory lesions: a dynamic equilibrium.

This essay is designed as a partial summary of the work of several students and colleagues from our laboratory. For the most part the experimental data have been published and this seminar represents an attempt to summarize, integrate and speculate on this work. In some situations the speculation is rather unrestrained and it is hoped that it will provoke discussion, controversy and better future experiments. Reference is made to the original articles and to recent reviews. In addition, since we have had the advantage of reading the other contributions to this volume, there is considerable reference to other chapters. We and others have argued in other publications that it is imperative to understand the normal physiological traffic of lymphocytes before one can adequately interpret data describing lymphocyte migration through pathological tissues. It has been useful to compare data derived from traffic through lymph nodes because there is considerable information on the individual lymph node with respect to blood-lymphocyte delivery and blood flow, prenodal input via peripheral lymphatics and, particularly in sheep, in the numbers and phenotypic analysis of the lymphocytes exiting lymph nodes in postnodal or efferent lymph (see Young, this volume). We consider the terms prenodal for afferent and post-nodal for efferent to be synonomous. In this volume, a significant contribution has been made by Cahill et al which describes the astonishing degree of lymphocyte traffic which occurs in fetal life prior to antigenic challenge. At the other extreme, in disease states, there is often profound activation of lymphocytes. This is most apparent in viral infections like HIV and SIV (Rosenberg et al, this volume) and also in the various models of diseases such as EAE (Hickey and Kulidjian et al, this volume). It is a central tenet of our paper that resting and activated lymphocyte migration need to be considered separately and that they are very different.

Animals↗
PubMed1998

A simple breathing circuit minimizing changes in alveolar ventilation during hyperpnoea.

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.

Adult↗
PubMed1996

PCO2 affects tracheal tone during apnea in anesthetized dogs.

We hypothesized that CO2, like hypoxia and withdrawal of pulmonary slowly adapting receptor input, would cause tracheal constriction during neural apnea (absence of phrenic activity). In seven anesthetized paralyzed dogs ventilated to neural apnea, we increased arterial PCO2 (PaCO2) in steps by adding CO2 to the inspirate while keeping ventilation constant. Increases in PaCO2 caused tracheal constriction during neural apnea in all dogs; 69 +/- 26 (SD)% of the change in tracheal diameter occurred during neural apnea. Average sensitivity of tracheal diameter to CO2 was 0.44 mm/Torr PaCO2. Our data suggest that central chemoreceptor inputs to brain stem neurons controlling smooth muscle of the extrathoracic airway bypass central mechanisms generating inspiration.

Animals↗
PubMed1994

Genomic structure of the candidate proto-oncogene BCL3.

We previously reported the identification of a novel candidate proto-oncogene involved in the translocation t(14;19)(q32;q13) found in some cases of human B-cell chronic lymphocytic leukemia. This gene, BCL3, is a member of the I kappa B family, whose encoded proteins regulate the NF-kappa B family of transcription factors. Here we describe the genomic structure of BCL3. The gene contains nine exons, spanning 11.5 kb. In comparison to other members of the I kappa B family, there is a remarkable conservation of the exon-intron boundaries in relation to the coding sequences, consistent with an origin from a common ancestral gene. BCL3 is unusual in containing two CpG islands, a 5' island encompassing the first exon, the other lying within the gene. Southern blot analysis using methylation-sensitive restriction enzymes revealed that while the 5' CpG is unmethylated in all tissues tested, the degree of methylation of the internal CpG island varies.

Amino Acid Sequence↗
PubMed1994

Increased incidence of second neoplasms in patients treated with interferon alpha 2b for hairy cell leukemia: a clinicopathologic assessment.

We report that there is an unexpectedly high incidence of second neoplasms in patients after treatment of hairy cell leukemia (HCL) with interferon alpha 2b (IFN). In a cohort of 69 patients with HCL entered in a protocol using IFN as the primary treatment, and followed thereafter for a median of 91 months (range, 0.2 to 109 months), 13 patients (19%) developed a second neoplasm. Six neoplasms were of hematopoietic origin, whereas the remaining seven were adenocarcinomas. The expected number of second tumors in this cohort is three (based on calculations from the National Cancer Institute's SEER data), so the excess frequency (observed:expected) is 4.33. However, the excess frequency is even greater for the hematopoietic neoplasms; the expected frequency is 0.15, whereas six hematopoietic tumors occurred, for an observed:expected ratio of 40. In general, the second neoplasms have behaved aggressively, and the median survival after diagnosis of the second neoplasm was only 8.8 months. Although we cannot entirely exclude the possibility that IFN therapy has some direct oncogenic effect, we suspect that increased frequency of second tumors is related to prolonged survival of patients who are immunocompromised because of HCL and thus prone to develop second tumors. If so, the frequency of second neoplasms in patients with HCL may be even greater in the future with continued improvements in therapy.

Adult↗