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Biomedical subjects

P Stewart

Publications and source records attributed to P Stewart.

At least 19 recordsLinked to original sources
PubMed1992

Secretion of breast gross cystic disease fluid proteins by T47D breast cancer cells in culture--modulation by steroid hormones.

The effect of steroid hormones on modulating the secretion rates of three human breast gross cystic disease fluid proteins (GCDFP-15, GCDFP-24, and GCDFP-44) by T47D breast carcinoma cells in tissue culture was evaluated. Androgens (dihydrotestosterone or fluoxymesterone) were capable of stimulating the secretion rates for all three GCDFP's while showing a minimal trend toward slowing the growth rate of T47D cells. This is the first study which shows that androgens can specifically stimulate all three of the major breast GCDFP's concomitantly. Progesterone, and three synthetic progestins, all showed inhibition of the growth rate of T47D cells while causing enhancement of the secretion of GCDFP-15 and GCDFP-44, and only minimal effect on the secretion rate of GCDFP-24. Estradiol was essentially neutral to the growth rate of the T47D cells in our test system. Estradiol did cause a mild enhancement of GCDFP-44 secretion rate, with no appreciable effect on GCDFP-15 or GCDFP-24 secretion rates. These findings suggest that an androgenic stimulus may be involved in the secretion of GCDFP's associated with breast gross cystic disease.

Adipokines↗
PubMed1992

The repetitive vascular catastrophes of Behçet's disease: a case report with review of the literature.

Behçet's disease is a chronic, recurrent disease that most commonly presents as oral and genital ulcers and iritis. It is a multisystem disease with possible cardiovascular, pulmonary, neurologic, cutaneous and articular involvement. It is most often diagnosed in the 20 to 40 year age group, and vascular and neurologic involvement worsens the prognosis. Vascular manifestations include venous and arterial occlusions, arterial aneurysm and pseudoaneurysm formation. We present the case of a young man with Behçet's disease with multiple aneurysms, pseudoaneurysms, arterial occlusions and venous thrombosis with a literature review. Surgeons must consider Behçet's disease when dealing with aneurysms in young patients.

Adult↗
PubMed1992

Functional and morphological changes induced by tunicamycin in dividing and confluent endothelial cells.

Cultured bovine aortic endothelial cells treated with tunicamycin, an inhibitor of glycoprotein synthesis, developed a concentration-dependent inhibition of N-acetylglucosamine-1-phosphate transferase activity, and this inhibition was correlated with a substantial decrease in [3H]mannose incorporation by the cells. Endothelial cells were very sensitive to tunicamycin, and changes in their morphology occurred as a result of the inhibition of glycoprotein synthesis. The cells became elongated, the surface irregular, roughened, and granular, and there was an increase in the interstitial space between the cells. Electron dense material was accumulated within and dilated the rough endoplasmic reticulum, and the distribution of the glycoproteins laminin and fibronectin throughout the endothelial cell monolayer was modified. These morphological changes coincided with functional impairment with the permeability of endothelial cell monolayers to both 125I-albumin and [3H]inulin being increased by treatment with tunicamycin (10(-6) M) for 24 h. These results indicate that the synthesis of glycoproteins is crucial for cell-cell adhesion and the functional properties of the endothelial lining of blood vessels.

Albumins↗
PubMed1992

Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody.

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.

Adult↗
PubMed1992

Lignin peroxidase gene family of Phanerochaete chrysosporium: complex regulation by carbon and nitrogen limitation and identification of a second dimorphic chromosome.

Lignin peroxidases (LiP) of Phanerochaete chrysosporium are encoded by a family of six closely related genes. Five LiP genes have been localized to the same dimorphic chromosome. In this investigation, relative transcript levels of the LiP genes were determined. Transcripts of the LiPA, LiPB, and O282 genes were at similar levels in both carbon- and nitrogen-limited cultures. In contrast, transcription of the GLG5, V4, and GLG4 genes was dramatically altered by culture conditions. Under carbon-limited conditions, GLG4 transcripts were, by far, the most abundant. Southern blot analyses of clamped homogeneous field gels were used to map the GLG4 gene to a dimorphic chromosome separate from the other LiP genes.

Base Sequence↗
PubMed1992

[Idiopathic dilatation of the right atrium diagnosed in utero].

It is described one case of extreme right atrium dilatation detected in utero, as an isolated abnormality. Ebstein's anomaly was first suspected because in-utero tricuspid regurgitation detected with Doppler two dimensional echocardiography. Soon after birth and thereafter no tricuspid regurgitation could be find and no symptoms are present, despite the giantly dilated right atrium. The aetiology of this abnormality is discussed and the benign course emphasized.

Adult↗
PubMed1991

A strychnine-sensitive site is involved in dynorphin-induced paralysis and loss of the tail-flick reflex.

Dynorphin A(1-13) administered intrathecally to rats induces a reversible hindlimb paralysis and permanent loss of the tail-flick reflex in a dose-dependent and all-or-none manner. The loss of the tail-flick reflex has been determined to result from neurotoxicity linked to the N-methyl-D-aspartate (NMDA) receptor. Recently, it has been reported that NMDA antagonists attenuate irreversible paralysis induced by dynorphin A(1-17) and dynorphin A(2-17). In the present studies, we examined whether repeated injections of dynorphin A(1-13) acetate salt could change the characteristics of the reversible paralysis. Injections repeated every 48 h resulted in hindlimb paralysis upon each injection which was not different in terms of magnitude or duration (P greater than 0.60). Injections repeated at 2 h intervals resulted in desensitization of the paralytic effects (P less than 0.05). We also examined if strychnine sulfate, a glycine antagonist would alter the paralytic response to dynorphin. Strychnine protected rats from paralysis (P less than 0.01) and loss of the tail-flick reflex with an ED50 of 7 nmol. We conclude that the reversible paralysis induced by dynorphin A(1-13) is repeatable which suggests that the paralysis results from nontoxic or subtoxic actions of dynorphin. Desensitization to the paralytic effects occurs with closely spaced injections by some unknown mechanism. In addition, we conclude that the spinal glycinergic inhibitory system may participate in the induction of the paralysis because strychnine antagonizes dynorphin-induced paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Consumer interest in alternatives to physician-centred hospital birth in Ottawa.

A survey of 1109 women who delivered in a hospital or at home in a major city in Canada was conducted. The women were asked to respond to questions concerning the type of health professional they would like to provide reproductive care. The choices they were offered were: midwife, obstetrician, general practitioner or nurse, or a combination. Respondents were also asked to identify if they had an interest in an alternative such as a birthing room, birthing centre or home birth, to hospital labour ward care. Almost 60% of women were interested in some form of midwifery care with the major emphasis placed on counselling and support. Of the women who expressed an interest in midwifery services a large number elected for that service to be shared with an obstetrician. Women who were older and had achieved a high level of education were more interested in midwifery services than other women. If given choices of a hospital labour, birthing room, birthing centre or home birth 53% of women would choose to give birth in a hospital labour ward. A major reason for this choice was the accessibility of epidural analgesia. The majority of women who had experienced a home birth would make the same choice again. There was a strong positive association between interest in using midwifery services and interest in a birthing centre and home birth.

Adolescent↗
PubMed1991

Pretreatment of the primigravid uterine cervix with mifepristone 30 h prior to termination of pregnancy: a double blind study.

OBJECTIVE: To determine the effect of the antiprogestogen mifepristone (RU 486) on cervical resistance before first trimester termination of pregnancy. DESIGN: Prospective double blind randomized placebo controlled study. SETTING: Department of gynaecology in a university teaching hospital, Sheffield. SUBJECTS: 80 Primigravid women greater than 18 years of age, undergoing termination of pregnancy at between 7 and 13 weeks gestation. INTERVENTIONS: A single dose of 600 mg of mifepristone or placebo given orally 30 h before termination of pregnancy under general anaesthesia. MAIN OUTCOME MEASURES: Cervical resistance to dilatation. RESULTS: Pretreatment with mifepristone significantly reduced the amount of force required to dilate the cervix to 10 mm. In comparison with placebo, the mean sum of the peak forces obtained with dilators 4 to 10 mm was reduced from 84.3 N (SD 29.7) to 46.0 N (SD 26.7). Two women in the treated group had a cervical resistance of greater than 100 N compared with nine women in the placebo group (RR 0.18, 95% CI 0.04-0.89). The 8 mm dilator could be passed with less than 5 N force in 16 women (43%) in the treated group compared with none in the placebo group. Women in the active treatment group had more preoperative pelvic pain and vaginal bleeding but less postoperative pain. CONCLUSION: Mifepristone significantly reduces cervical resistance in the first trimester of pregnancy and produces minimal side effects.

Abortion, Therapeutic↗
PubMed1991

Dynorphin-induced depression of the dorsal root potential in rat spinal cord: a possible mechanism for potentiation of the C-fiber reflex.

Dynorphin A (1-13) acetate salt was applied to the exposed spinal cord of rats during electrophysiological recording of the dorsal root potential (DRP) and the DR III arising from dorsal root stimulation. Simultaneously, ventral root potentials indicative of monosynaptic and polysynaptic myelinated pathways were recorded. Amplitudes of the DRP and DR III were decreased for 30 to 60 min in a dose-dependent manner after dynorphin administration with ED50 values of 21 and 28 nmol, respectively. Amplitude of ventral root potentials was also decreased with a maximal effect at 5 min postdrug treatment. In contrast, we (Caudle and Isaac, J. Pharmacol. Exp. Ther. 246: 508-513, 1988b) showed that the polysynaptic unmyelinated pathway (C-fibers) was greatly enhanced by dynorphin treatment and that this pathway was the locus of excitotoxicity (Caudle and Isaac, Brain Res. 443: 329-332, 1988a). Because the DRP reflects gamma-aminobutyric acid-mediated presynaptic inhibition of primary afferent terminals, these data indicate that dynorphin suppresses gamma-aminobutyric acid-mediated inhibition thereby disinhibiting primary afferent transmission. This presynaptic disinhibition may be the mechanism for the selective potentiation of the C-fiber pathway which may account for the selective neuron toxicity, i.e., loss of the C-fiber pathway and sparing of the monosynaptic and polysynaptic myelinated pathways after dynorphin administration.

Action Potentials↗
PubMed1991

Prophylaxis of graft-versus-host disease by administration of the murine anti-IL-2 receptor antibody 2A3.

The efficacy of murine monoclonal IgG1 antibody 2A3 specific for the 55 kD chain of the human IL-2 receptor (CD25) was evaluated for prophylaxis of acute GVHD in patients with advanced leukemia transplanted with unmodified bone marrow from related HLA-haploidentical donors incompatible for two or three HLA loci of the nonshared haplotype. As GVHD prophylaxis, 36 patients (control) received standard cyclosporine and methotrexate (C + M) whereas 11 patients (study) received C + M plus antibody 2A3, 1.0 mg/kg on day -1, and 0.5 mg/kg daily from day 0 through day +19. Antibody administration was not associated with appreciable toxicity and did not adversely affect engraftment. During treatment, circulating CD25+ cells appeared saturated by the infused antibody. Patients receiving antibody 2A3 tolerated more cyclosporine than controls (p less than 0.001) with lower increase of serum creatinine (p less than 0.05) during the first month. Seven of 10 (70%) evaluable study patients developed acute GVHD of grade II-IV with onset at a median of 20 days compared to 27 of 31 (87%) control patients with onset at a median of 13 days (p = 0.11). Trough serum levels of antibody 2A3 ranged from 7.2 to 68.8 mg/l, and lower values correlated with occurrence of acute GVHD. A human anti-mouse immunoglobulin antibody response was detected in four patients but was not associated with lower levels of antibody 2A3 in the serum. Two study patients and two controls have survived more than 1 year (p = 0.92). These findings suggest that administration of antibody 2A3 suppressed and delayed activation of alloantigen-specific T cells but did not result in their elimination.

Adolescent↗
PubMed1990

MK-801 blocks dynorphin A (1-13)-induced loss of the tail-flick reflex in the rat.

Dynorphin A (1-13) administered intrathecally to rats results in a dose-dependent loss of the tail-flick reflex. This effect is mediated, at least in part, by N-methyl-D-aspartate receptors. We examined the influence of pretreatment or post-treatment with MK-801 on this behavioral response. MK-801 administered i.p. 30 min prior to dynorphin provided dose-dependent protection against loss of the tail-flick reflex with an ED50 of 0.06 mg/kg. MK-801 administered after dynorphin had a dose- and time-dependent protective action. The dose of 0.06 mg/kg protected 63% of the animals from loss of the tail-flick reflex when injected 15 min after dynorphin. In contrast, 3 mg/kg did not protect animals when injected 15 min after dynorphin, but did protect 50% of the animals when injected 30 min post-dynorphin. Although we cannot exclude other effects mediated by MK-801, these data support our previous findings that dynorphin-induced loss of the tail-flick reflex involves the N-methyl-D-aspartate-receptor complex and support the contention that the process(es) initiated by dynorphin injection proceed rapidly (minutes rather than hours).

Animals↗
PubMed1990

What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?

One hundred forty-seven consecutive patients with leukemia, myelodysplastic syndrome, or aplastic anemia were treated by marrow grafts from genotypically HLA-identical siblings (n = 122) or HLA-haploidentical family members (n = 25). Haploidentical recipients differed from their donors for no more than one HLA locus on the nonshared haplotype. All were given postgrafting immunosuppression with a combination of methotrexate and cyclosporine. In a randomized study we explored whether prednisone administered from day 0 through 35 along with methotrexate/cyclosporine could improve prevention of acute graft-versus-host disease (GVHD). The GVHD incidence in patients not given prednisone was comparable with that previously reported with methotrexate/cyclosporine. Unexpectedly, significant increases in acute and also chronic GVHD were seen in HLA-identical recipients administered prednisone, but not in the small number of patients administered HLA-nonidentical grafts. However, the resultant increase in transplant-related mortality in patients administered prednisone was offset by an increase in leukemic relapse in patients not administered prednisone, presumably related to the absence of a graft-versus-leukemia effect. Therefore, overall disease-free survival of the two groups of patients was comparable, with slightly more than 50% of the patients being alive at more than 2 years after transplantation. We speculated that prednisone adversely affected GVHD prophylaxis, interfering with methotrexate's cell cycle-dependent suppression of donor lymphocyte proliferation in response to host antigens. In a pilot study we explored whether beginning prednisone on day 15, after completion of methotrexate administration, would avoid this adverse effect. The GVHD incidence in patients administered methotrexate/cyclosporine along with "late" prednisone was comparable with that in patients not administered prednisone. We conclude that methotrexate/cyclosporine is effective in decreasing the incidence of grade II through IV GVHD, and that the addition of prednisone to this regimen is not beneficial in recipients of HLA-identical marrow grafts.

Acute Disease↗