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Biomedical subjects

J Wells

Publications and source records attributed to J Wells.

At least 145 records · Page 8Linked to original sources
PubMed1986

Intrathecal morphine and heroin in humans: six-hour drug levels in spinal fluid and plasma.

Lumbar spinal fluid and plasma concentrations of morphine were measured by radioimmunoassay after intrathecal administration of 1 mg of morphine (n = 13) or heroin (n = 10). Plasma levels of morphine were measured regardless of 'whether heroin or morphine was injected intrathecally, because of the rapid biotransformation of heroin to morphine in plasma. Significant drug concentrations appeared in plasma after intrathecal heroin (peak concentration 47.8 +/- 9.0 nmol/L, time to peak concentration 10 +/- 2.4 min); after intrathecal morphine plasma drug concentrations were significantly lower (8.1 +/- 1.0 nmol/L; P less than 0.002) and significantly later (216 +/- 39 min; P less than 0.002). Elimination half-life of heroin from spinal fluid (43 +/- 5 min) was significantly shorter than for morphine (73 +/- 5 min; P less than 0.02).

Aged↗
PubMed1986

Model system for removing neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads.

Variables effecting removal of neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads were studied. Human neuroblastoma cell lines were labeled with the supravital DNA stain Hoechst 33342, seeded into normal bone marrow, incubated with monoclonal antibodies recognizing neuroblastoma cell surface antigens (HSAN 1.2, antibody 459, antibody 390, BA-1, and Leu-7), and then mixed with magnetic microspheres coated with goat anti-mouse immunoglobulin. Tumor cells that attached to the magnetic immunobeads were then removed from the marrow with magnets. The efficacy of tumor cell removal depended on the amount of monoclonal antibody bound to tumor cells and the immunobead/tumor cell ratio. In addition, two cycles of purging with both monoclonal antibodies and immunobeads was superior to one cycle. Using a cocktail of the five antibodies, 3 to 4 logs of tumor cells could be depleted from marrow with good recovery of viable hematopoietic cells.

Antibodies, Monoclonal↗
PubMed1986

Defendants with repeated competency evaluations.

In order to clarify the nature of those defendants referred multiple times for competency-to-stand-trial evaluations, 390 consecutive admissions to the Yale-New Haven Psychiatric Court Clinic were reviewed. Fifty-four of these had had more than one evaluation in the 2.5-year period under study and will be referred to as repeaters. Repeaters were significantly different from nonrepeaters in terms of diagnosis (p less than .01), tending to be more likely to be schizophrenic or affectively disordered. Repeaters also tended to have less education (p less than .01) and to be found competent less often (p less than .01) than nonrepeaters. No repeater-nonrepeater differences were found in age, race, or legal charge. Implications for future research on and management of this population are discussed.

Adult↗
PubMed1985

Cross-species embryonic septal transplants: restoration of conditioned learning behavior.

Embryonic septal and hippocampal tissue from mice was transplanted between species into the brains of adult rat hosts as cell suspensions. Deficits in the ability to learn a conditioned, hippocampally mediated, forced alternation behavior, which were caused by a bilateral transection of the fornix-fimbria pathway, were ameliorated in the septal transplant recipients. The successful performance of the task was correlated to the density index of acetylcholinesterase in the hippocampal section.

Acetylcholinesterase↗
PubMed1985

192Ir pharyngoepiglottic fold interstitial implants. The key to successful treatment of base tongue carcinoma by radiation therapy.

Twenty-eight patients with squamous carcinomas of the base tongue were seen and evaluated in a conjoint Head and Neck Tumor Board at Stanford between 1976 and 1982. Fourteen patients were treated by combined external beam and interstitial irradiation, 11 of whom had Stage III and IV carcinomas (American Joint Committee). An initial dose of 5000 to 5500 rad was first delivered by external beam irradiation in 5 to 5.5 weeks, followed approximately 3 weeks later by an iridium 192 (192Ir) interstitial implant boost by the trocar and loop technique. The key to successful treatment of these neoplasms was found to be the use of a lateral percutaneous cervical technique, which placed horizontal loops through the oropharyngeal wall above and below the hyoid bone; the superior loop included the pharyngoepiglottic fold and the tonsilloglossal groove. Standard multiple loop implants (submentally inserted) of the base tongue from the vallecula anteriorly to the circumvallate papillae were also used routinely. This approach has been successful, since 10 of the 14 patients (71%) remain without evidence of disease (mean follow-up, 32 months). There have been only two local recurrences, both on the pharyngoepiglottic fold in patients who did not receive the now standard pharyngoepiglottic fold/lateral pharyngeal wall implants. No patients have relapsed after 18 months. The other 14 patients were treated prospectively during the same period by combining initial resection, radical neck dissection, and postoperative irradiation. In this group, there were more locoregional failures compared to the group treated with radiation therapy alone (5 tongue recurrences and 7 neck relapses); in addition, more severe complications were noted in these 14 patients who received surgery and postoperative irradiation. The authors believe that combined external beam and interstitial irradiation is effective treatment for base tongue carcinomas, especially when the high-dose distribution includes the adjacent tonsilloglossal groove, pharyngoepiglottic fold, and oropharyngeal wall to and below the level of the hyoid bone, in addition to treating an adequate base tongue volume.

Brachytherapy↗
PubMed1985

Cross-species neural transplants of embryonic septal nuclei to the hippocampal formation of adult rats.

In the absence of immunosuppressive treatment, suspensions of cells from the developing septal region of mouse embryos were transplanted successfully into the denervated hippocampal formations of adult rat hosts. The longitudinal recovery of acetylcholinesterase (AChE)-containing fibers in the host was the index of transplant success. In transplant recipients, the fornix-fimbrial interconnection between the septum and hippocampal formation was severed unilaterally, and two 5 microliter aliquots of cell suspension were injected into the hippocampal formations of host rats. Five sets of controls included one in which animals received no surgical intervention (Normal Controls), and another which was subjected to a sham operation (Sham Controls). The fornix-fimbria pathway was transected unilaterally in Lesion Control animals, while Hippocampal Controls received the same lesion plus two injections of non-cholinergic cells from the hippocampal formations of mouse embryos. Injection Controls were subjected to a fornix-fimbria transection and given two injections of debris and dead cells in saline. The cross-species transplants induced the return of a normal AChE laminar pattern in the recipient rats. The density of the laminar pattern, quantified with laser densitometry, was greatest in transplants that had survived for one week, but only in sections adjacent to the injection sites. Although the density decreased from the first through third weeks of survival, overall density of AChE staining stabilized from the fourth through 17th weeks of survival. Because the success rates of these cross-species transplants were similar to those reported for homogenic tissue, it was concluded that the rat brain is a suitable host for xenogenic transplants of septal neurons from embryonic mice.

Acetylcholinesterase↗
PubMed1985

Inertial force as a possible factor in mitosis.

Some previous studies of cell division have suggested that chromosome movements in mitosis involve two distinct forces: one which pulls chromosomes poleward by means of attached fibers, and another which tends to push chromosome arms away from the pole. The latter force may also be a factor in non-chromosomal spindle transport, by which objects other than chromosomes are transported toward or away from spindle poles. Based on a survey of previous literature, this paper makes a prima facie case for describing this latter force as "inertial", since in some respects it can be simulated by centrifugation. A theoretical analysis demonstrates that an inertial force could arise in the spindle from postulated high-frequency, small-amplitude oscillations, which could be caused by changes in coherently processing electron spin alignments at the spindle poles. Some possible experimental approaches to the problem are briefly outlined.

Biophysical Phenomena↗
PubMed1985

Stimulation of Na+/H+ antiport is an early event in hypertrophy of renal proximal tubular cells.

Renal hypertrophy in vivo is achieved by an increase in protein content per cell and an increase in cell size with minimal hyperplasia. Hypertrophied renal tubular cells remain quiescent and demonstrate an increase in transcellular transport rates. This situation was simulated in vitro by exposing a confluent, quiescent primary culture of rabbit renal proximal tubular cells to either insulin, prostaglandin E1, or hypertonic NaCl for 24 or 48 hr. Protein per cell increased by 20-30% with little or no increase in [3H]thymidine incorporation into DNA. Mean cell volume was also increased in insulin- and hypertonic NaCl-treated but not in prostaglandin E1-treated cells. The lag period required to initiate DNA synthesis by a combination of insulin and hydrocortisone was the same in control and hypertrophied cells, indicating a quiescent state of the latter. Two hours of exposure to the growth stimuli increased amiloride-sensitive Na+ uptake, Na-dependent H+ efflux, and ouabain-sensitive Rb+ uptake, indicating that stimulation of Na+/H+ antiport (exchange) occurs as an early event in their action. Hypertrophied cells continued to demonstrate enhanced Na+/H+ antiport after the growth stimuli were removed for 3 hr, by which time their acute effects are reversed.

Alprostadil↗
PubMed1985

A monokine stimulates production of human erythroid burst-promoting activity by endothelial cells in vitro.

Conditioned media were prepared from human peripheral blood monocytes and human umbilical vein endothelial cells. These media were assayed for erythroid burst-promoting activity (BPA) using human peripheral blood monocyte-depleted mononuclear cells as targets and assessing the stimulatory effect of the conditioned media on growth of early erythroid progenitor cells. Both monocytes and endothelial cells produced modest amounts of detectable BPA. Addition of varying concentrations of media conditioned by monocytes to plateau concentrations (5-10%) of media conditioned by endothelial cells had no additive effect. Endothelial cells incubated in the presence of 50% monocyte-conditioned medium produced 2.5- to 6.6-fold more BPA than did endothelial cells incubated only in control tissue culture medium. In contrast, endothelial cell conditioned medium did not stimulate increased BPA production by monocytes. Neither neutrophil- nor marrow fibroblastoid cell-conditioned medium stimulated BPA production by endothelial cells. Therefore, both monocytes and endothelial cells produce BPA. Moreover, monocytes produce a monokine that, in turn, stimulates the production of BPA by endothelial cells. Inasmuch as a monokine also has been shown to stimulate production of granulocyte-macrophage colony-stimulating activity, we propose that monocytes play a critical role in regulating the production of humoral regulators of the very early stages of hemopoietic cell differentiation.

Culture Media↗
PubMed1985

Inhibition of collagen deposition in the extracellular matrix prevents the establishment of a stroma supportive of hematopoiesis in long-term murine bone marrow cultures.

Long-term production of murine hematopoietic cells in vitro is dependent on establishment of a complex microenvironment consisting of a variety of stromal cells and an extensive extracellular matrix which includes collagen, fibronectin, laminin, proteoglycans, and other undefined components adherent to the culture dishes. Cis-4-hydroxyproline (CHP), a relatively specific inhibitor of collagen secretion, was used to examine the role of extracellular collagen deposition in supporting hematopoiesis in long-term C57B1/6J mouse bone marrow cell cultures. Throughout the 10-wk culture period, all culture dishes contained either 0, 10, 25, or 50 micrograms/ml of CHP. All medium and nonadherent cells were removed at weekly intervals and replaced with fresh medium containing the previous concentrations of CHP. Nonadherent cells were assayed weekly for total cells and pluripotent, erythroid, megakaryocytic, and granulocytic-macrophage progenitor cells. Dishes were killed at selected intervals to assess protein and collagen synthesis in the adherent layer. Adherent cell numbers, as judged by microscopic examination and DNA assays, correlated inversely with CHP concentrations used and paralleled degree of collagen synthesis inhibition. The decreased hemopoietic progenitor cell production correlated closely with percent inhibition of collagen synthesis and stromal cellularity. The CHP concentrations tested were not directly toxic to hemopoietic progenitor cells. These studies demonstrate that collagen deposition in the extracellular matrix of murine bone marrow cell cultures is essential to the establishment of a functional stromal microenvironment that is supportive of long-term hematopoiesis.

Animals↗
PubMed1985

An evaluation of fused silica capillary columns for the screening of basic drugs in postmortem blood: qualitative and quantitative analysis.

Fused silica capillary columns (Durabond) have been evaluated for the screening of more than 100 basic drugs in postmortem blood samples. The combination of these columns, nitrogen-phosphorus detectors, and SKF-525A (internal standard) allows for the simultaneous screening and quantitation of several basic drugs such as amphetamines, amitriptyline, and codeine. Approximately 2000 blood samples have been analyzed by this procedure. The use of capillary columns results in excellent baseline stability and this, together with an autosampler and data system, enables unattended overnight operation. "Double peaking" associated with splitless injection can be a problem as can sensitivity for some of the polar drugs; however, with the extraction procedure described and the equipment used, the screening of blood for basic drugs is improved when compared with packed column technology.

Chromatography, Gas↗
PubMed1985

Late nonstochastic changes in pig skin after beta irradiation.

Late radiation-induced changes in pig skin have been assessed following irradiation with beta-rays from a 22.5- or 15-mm-diameter 90Sr/90Y source and a 19- or 9-mm-diameter 170Tm source. Late damage, in terms of dermal atrophy, was assessed 2 years after irradiation from measurements of dermal thickness in irradiated and normal skin. After 90Sr irradiation maximum atrophy, a dermal thickness of 40-50% of the control value, occurred at a dose of approximately 40 Gy from the 22.5-mm source and approximately 75 Gy from the 15-mm source. In the case of 170Tm the 19- and 9-mm sources produced similar degrees of atrophy at equal doses. Maximum atrophy occurred at approximately 70 Gy, when the dermis was approximately 70% of the thickness of normal skin. Significant late tissue atrophy was seen at doses, from both types of radiation, which only produced minimal erythema in the early reaction. Such late reactions need to be taken into account when revised radiological protection criteria are proposed for skin.

Animals↗