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Biomedical subjects

N Siegel

Publications and source records attributed to N Siegel.

At least 19 recordsLinked to original sources
PubMed2001

Promegapoietin-1a, an engineered chimeric IL-3 and Mpl-L receptor agonist, stimulates hematopoietic recovery in conventional and abbreviated schedules following radiation-induced myelosuppression in nonhuman primates.

Promegapoietin-1a (PMP-1a), a multifunctional agonist for the human interleukin 3 and Mpl receptors, was evaluated for its ability to stimulate hematopoietic reconstitution in nonhuman primates following severe radiation-induced myelosuppression. Animals were total body x-irradiated (250 kVp) to 600 cGy total midline tissue dose. PMP-1a was administered s.c. in several protocols: A) daily (50 microg/kg) for 18 days; B) nine doses (5 microg/kg) every other day for 3 weeks; C) a single high dose (100 microg/kg) at 20 hours, or D) a single high dose (100 microg/kg) at 1 hour following TBI. The irradiation controls received 0.1% autologous serum for 18 consecutive days. Hematopoietic recovery was assessed by bone marrow clonogenic activity, peripheral blood cell nadirs, duration of cytopenias, time to recovery to cellular thresholds, and requirements for clinical support. PMP-1a, irrespective of administration schedule, significantly improved all platelet-related parameters: thrombocytopenia was eliminated, the severity of platelet nadirs was significantly improved, and recovery of platelet counts to > or =20,000/miccrol was significantly reduced in all PMP-1a-treated cohorts. As a consequence, all PMP-1a-treated cohorts were transfusion-independent. Neutrophil regeneration was augmented in all treatment schedules. Additionally, all PMP-1a-treated cohorts showed an improvement in red blood cell nadir and recovery. PMP-1a in conventional or abbreviated schedules induced significant thrombopoietic regeneration relative to the control cohort, whereas significant improvement in neutrophil recovery was schedule-dependent in radiation-myelosuppressed nonhuman primates.

Animals↗
PubMed2000

Bacteriology of nontraumatic maxillary sinus mucoceles versus chronic sinusitis.

OBJECTIVE: To compare the bacteriology of maxillary sinus mucoceles to chronic sinusitis and understand the pathogenesis of nontraumatic maxillary sinus mucoceles (NTMSM). STUDY DESIGN: Retrospective review. METHODS: Review of intraoperative bacteriology culture results obtained in patients with NTMSM. Patients with history of facial trauma or previous paranasal sinus surgery were not included in the study. The results were compared to intraoperative cultures obtained from patients with chronic sinusitis (CS). RESULTS: The study groups consisted of 16 patients with NTMSM (9 male and 7 female patients) and 211 patients with CS (86 male and 125 female patients). Cultures in the NTMSM group were positive in 7 of 16 patients (44%) (four cultures had more than one isolate). There was no growth in cultures of 9 patients (56%). On the other hand, cultures in 176 patients with CS (83%) grew organisms (42 cultures had more than one isolate); there was no growth in 35 of 211 patients (17%) (P = .0007). The cultures grew aerobic bacteria in 7 of 16 (44%) and 160 of 211 (76%) patients of the NTMSM and CS groups, respectively. Anaerobic bacteria were detected in cultures of 2 of 16 patients (12.5%) with NTMSM compared with 13 of 211 patients (6.2%) in the CS group (P = .286). The most common pathogenic aerobe in the NTMSM group was alpha-hemolytic Streptococcus, while Staphylococcus aureus was the most common in the CS group. CONCLUSION: The bacteriology of maxillary sinus mucoceles is different from that of CS. The majority of patients with mucoceles have sterile intraoperative cultures. The data do not support infection as the main origin of NTMSM.

Adult↗
PubMed1997

Attenuation of IL-5-mediated signal transduction, eosinophil survival, and inflammatory mediator release by a soluble human IL-5 receptor.

A soluble form of the human IL-5R alpha-chain (IL-5Ra) that contains the extracellular IL-5 binding domain has been evaluated for its effect on IL-5 binding to and activation of human eosinophils and basophils. The truncated receptor was expressed in Escherichia coli and recovered in biologically active form following renaturation and anion exchange chromatography. The soluble receptor formed a 1/1 complex with IL-5 in solution and bound IL-5 with affinity comparable to that of cell-associated IL-5Ra. Soluble IL-5Ra also competed with IL-5 for binding to the native alpha beta IL-5R on human cells and inhibited IL-5-mediated receptor activation and inflammatory mediator production. In this regard, the soluble receptor prevented IL-5-induced tyrosine phosphorylation of JAK2 kinase and IL-5R beta-chain and inhibited IL-5 priming of leukotriene C4 release by human basophils. However, the E. coli-derived receptor failed to inhibit IL-5 in longer term assays, including eosinophil survival and TF-1 cell proliferation, possibly due to its propensity to aggregate in a time- and temperature-dependent manner. In contrast, we observed that a soluble IL-5Ra derived from baculovirus-infected cells was less prone to aggregate and effectively antagonized IL-5-induced cell proliferation and survival. These findings indicate that the extracellular portion of the human IL-5Ra chain can prevent association of IL-5 with cell surface receptors and can attenuate signal transduction, mediator release, and survival of inflammatory cells. As such, soluble IL-5R may be useful in treating diseases such as human asthma, in which pulmonary injury is associated with the activity of IL-5R-bearing cells.

Basophils↗
PubMed1995

Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity.

Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates recovery of renal function. This effect is not related to global improvement in cell integrity. To determine the mechanism by which recovery of cellular ATP is enhanced, the effect of T4 on mitochondrial ATP production was evaluated using specific inhibitor stop assays for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T4 (20 micrograms/kg) during the reflow period. By 30-min reflow; the values for apparent endpoint of phosphate transport (PiTm, nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic animals (10.3 +/- 0.9) and remained stable at 120 min. T4 treatment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0) reflow compared with nonischemic control rats (24.7 +/- 2.4). T4 significantly improved ADPTm by 30 min (10.1 +/- 0.6, P < 0.05). By 120 min T4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed nonischemic control values. These data suggest the following: 1) postischemic mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which exceeds control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1993

Clinical manifestations of trichomoniasis in men.

OBJECTIVE: To determine the prevalence and clinical manifestations of trichomoniasis among sexually active men. DESIGN: Survey of two groups of men attending a sexually transmitted disease clinic. Subjects had a comprehensive sexual history and clinical examination plus cultures for Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis. PARTICIPANTS: The study included 147 sexual partners of women with trichomoniasis and 300 subjects selected randomly from heterosexual men coming to the same clinic for evaluation of new problems. MAIN OUTCOME MEASURES: Isolation of T. vaginalis was compared with urogenital signs and symptoms. RESULTS: The prevalence of T. vaginalis was 33 of 147 (22% [95% CI, 16% to 29%]) among sexual contacts of women with trichomoniasis and 17 of 300 (6% [CI, 3% to 9%]) among heterosexual men attending the same clinic. Men with trichomoniasis alone were more likely to complain of urethral discharge (P < 0.01), to have discharge on examination (P < 0.03), and to have inflammatory cells in their urethral secretions (P < 0.01) than were men who did not have T. vaginalis, N. gonorrhoeae, or C. trachomatis. Trichomonas vaginalis remained associated with nongonococcal nonchlamydial urethritis (adjusted odds ratio 3.8; CI, 1.1 to 11.2) after adjustment for race, age, number of sex partners in the previous 6 months, exposure to a partner with trichomoniasis, and history of trichomoniasis, urethritis, or gonorrhea. CONCLUSIONS: Trichomoniasis was common among men at risk for sexually transmitted diseases and was associated with symptoms and signs of urethritis.

Adolescent↗
PubMed1993

Glidewire treatment of resistant coronary occlusions.

Inability to cross the site of occlusion with a guidewire is the most common cause of failed angioplasty. The Glidewire, a kink-resistant, flexible wire with a hydrophilic coating, was applied to 71 (59 total, 12 subtotal) refractory occlusions, resulting in an overall angioplasty success rate of 45%. The Glidewire may improve the success rate for PTCA of total and subtotal occlusions that cannot be crossed with conventional guidewires.

Angina Pectoris↗
PubMed1993

Natural history of urogenital trichomoniasis in men.

Although Trichomonas vaginalis is a common sexually transmitted pathogen, the significance and natural history of trichomoniasis remain undefined in the male patient. We conducted a longitudinal study to examine the relationship of T. vaginalis to nongonococcal urethritis in men and to increase our understanding of the natural history of this infection. As previously reported, T. vaginalis was isolated from 50 of 447 men attending a sexually transmitted disease clinic by culture of urethra, first-void urine or external genitalia. Semen cultures proved valuable for documentation in select cases, including 4 instances when concomitant cultures of the external genitalia, urethra and first-void urine sediment were all negative. Spontaneous resolution was documented in 36% of untreated men but 1 asymptomatic man had persistence of T. vaginalis throughout a 4-month period. Nongonococcal nonchlamydial urethritis was documented in 12 of 21 men (57%) at the visit before treatment or spontaneous resolution compared to only 2 (10%) after elimination of T. vaginalis (p < 0.001). These findings suggest that spontaneous resolution of trichomoniasis and prolonged asymptomatic carriage occur in men with trichomoniasis and that T. vaginalis is a treatable cause of urethritis among sexually active men.

Adult↗
PubMed1992

Processing of atriopeptin prohormone by nonmyocytic atrial cells.

Atriopeptin (AP) is synthesized and stored in the mammalian atria as a 126 amino acid prohormone (AP126). Upon secretion, the prohormone undergoes site specific proteolysis within the atria to yield the carboxyl terminal 28 amino acid hormone (AP28). The atrial cell responsible for AP126 bioactivation has not yet been determined. Primary neonatal rat atrial cell cultures were generated with and without depletion of nonmyocytic cells. The molecular form of AP detected in the conditioned media of mixed cultures was determined to be AP126. Addition of dexamethasone to these cultures resulted in the appearance of a peptide that co-migrated with AP28. In contrast, no AP126 processing was detected in the conditioned media of myocyte enriched cultures when grown in the presence of dexamethasone. Readdition of nonmyocytic atrial cells to myocyte enriched cultures successfully reconstituted the steroid induced AP126 processing. Incubation of recombinant AP126argarg with nonmyocytic atrial cell cultures resulted in the generation of AP28argarg. We conclude that a nonmyocytic atrial cell is responsible for AP126 processing in vitro.

Animals↗
PubMed1992

Risk assessment and laboratory diagnosis of trichomoniasis in men.

Control of Trichomonas vaginalis is assuming higher priority because recent studies have suggested that trichomoniasis enhances susceptibility to human immunodeficiency virus infection and the risk for delivery of low-birth weight infants. In a cross-sectional study, 50 cases were identified among 447 men attending a sexually transmitted disease clinic. As previously reported, trichomoniasis was associated with nonchlamydial nongonococcal urethritis. Other risk factors included sexual contact with an infected woman or prior treatment for trichomoniasis or nongonococcal urethritis. Urethral and first-void urine cultures were positive in 80% and 68% of positive cases, respectively. When combined, these two cultures diagnosed 49 (98%) of 50 cases. These data suggest that criteria for selection of men for culture should include presence of nonchlamydial nongonococcal urethritis, recent exposure to trichomoniasis, or a history of trichomoniasis or nongonococcal urethritis. In addition, combining urethral and urine sediment cultures may prove accurate for evaluating T. vaginalis infection.

Adolescent↗
PubMed1989

Human vascular permeability factor. Isolation from U937 cells.

Human vascular permeability factor (hVPF) is a glycoprotein that promotes fluid and protein leakage from blood vessels. The function of hVPF is at present unknown, but the potent bioactivities of this protein suggest that it could act during inflammation, wound healing, and tumor angiogenesis. hVPF was purified from serum-free conditioned medium of the human histiocytic lymphoma cell line U937 as a disulfide-linked dimeric 40-kDa protein that promoted dermal blood vessel leakage in guinea pigs at a dose of 20 ng (3 x 10(-9) M) and promoted in vitro endothelial cell growth at concentrations as low as 50 PM. Multiple forms of hVPF with apparent pI values greater than 7.5 were resolved using pH gradient electrophoresis. Antibodies against guinea pig vascular permeability factor were found to cross-react with hVPF. The N-terminal amino acid sequence of hVPF was similar to, but not identical with, the N-terminal sequence of guinea pig vascular permeability factor.

Amino Acid Sequence↗
PubMed1988

Regulation of fibroblast cyclooxygenase synthesis by interleukin-1.

We have prepared polyclonal antiserum against sheep seminal vesicle prostaglandin H synthase (also termed cyclooxygenase) which cross-reacted with human cyclooxygenase, thereby enabling us to directly determine the synthetic rate of cyclooxygenase protein and its modulation by the monokine interleukin-1 (IL-1). Cultured human dermal fibroblast cells were labeled with [35S]methionine, and the membrane-bound cyclooxygenase was solubilized and immunoprecipitated 35S-labeled fibroblast cyclooxygenase migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular size of approximately 73,000 daltons, similar to that of native sheep cyclooxygenase and of cyclooxygenase covalently labeled by [3H]aspirin, i.e. [3H]acetylcyclooxygenase. Additional validation of the immunoprecipitated 35S-labeled cyclooxygenase band indicated that it was specifically displaced by unlabeled sheep cyclooxygenase. N-terminal amino acid radiosequence analysis of [3H]proline-labeled cyclooxygenase revealed [3H]proline residues in positions 3, 6, and 8, consistent with the previously reported N-terminal sequence of sheep cyclooxygenase. Endoglycosidase H treatment of 35S-labeled fibroblast cyclooxygenase caused a decline in apparent molecular size (due to removal of mannose residues) which was similar to that seen with the native sheep cyclooxygenase. [35S]Methionine pulse-chase experiments indicated a half-life of 1 h for fibroblast cyclooxygenase. The monokine interleukin-1 stimulated fibroblast cyclooxygenase synthesis in a time- and dose-dependent fashion; as little as 0.03 unit/ml of IL-1 produced significant stimulation of 35S-labeled cyclooxygenase synthesis. Maximum stimulation was 3-10-fold after preincubation of the cells with 0.3 unit/ml of IL-1 for 12-16 h. IL-1 treatment of cells yielded parallel dose-response curves for stimulation of prostaglandin E2 formation, increased cellular cyclooxygenase activity, and increased synthetic rate of newly formed cyclooxygenase, suggesting that the IL-1 effect is mediated mainly, if not solely, via induction of cyclooxygenase synthesis.

Animals↗
PubMed1988

Manipulation of stretch-induced atriopeptin prohormone release and processing in the perfused rat heart.

Atriopeptin (AP) is stored as the prohormone AP-126 [atrial natriuretic factor-(1-26)] in atrial granules. Cultured atrial myocytes synthesize and release only prohormone into the medium. HPLC analysis of the coronary venous effluent of media from perfused rat hearts subjected to right atrial stretch indicated the presence of the C-terminal mature hormone AP-28 [atrial natriuretic factor-(99-126)] and little or no prohormone. Absence of calcium from the perfusion medium increased total AP release and surprisingly blocked the proteolytic cleavage of the prohormone. Similarly, addition of the proteolytic inhibitor aprotinin to the perfusion medium suppressed the processing of the endogenous AP-126 released by atrial stretch. Aprotinin would be restricted to the extracellular space, which is therefore implicated as the site of prohormone processing. This suggestion was validated by the demonstration that the perfused rat heart could readily cleave exogenous prohormone to mature hormone, a process blocked by aprotinin. Hypothetically, the stimulus-release-processing event initiated by atrial stretch may require the concerted action of the synthetic cell (i.e., atrial myocyte) and a processing cell or site (e.g., the adjacent atrial mesenchymal cell) for the production of the mature AP-28, which is the circulating molecular form of this endocrine system.

Animals↗
PubMed1986

Parathyroid hormone stimulates dephosphorylation of the renoredoxin component of the 25-hydroxyvitamin D3-1 alpha-hydroxylase from rat renal cortex.

Parathyroid hormone (PTH) stimulates the renal conversion of 25-OH-vitamin D3 to 1,25-(OH)2-vitamin D3 in young animals. There is evidence that PTH acts via cAMP and cAMP-dependent protein kinase, but the identity of the phosphorylated protein(s) is unknown. The present study investigates the possibility that phosphorylation modification of specific components of the renal mitochondrial, cytochrome P-450-linked 25-OH-vitamin D3-1 alpha-hydroxylase is involved in the regulation of 1,25-(OH)2-vitamin D3 production. Mitochondria were isolated from [32P]phosphate-labeled renal cortical slices which had been divided into control and agonist-treated groups. The hydroxylase protein components from the solubilized mitochondria were partially purified using p-chloroamphetamine-Sepharose affinity chromatography and polyacrylamide gel electrophoresis. Phosphorylation was observed only in a protein with an Mr = 12,000 and a pI of 4.2 by autoradiography of the gels. This radiolabeled protein was immunoprecipitated with adrenodoxin antibody. Additionally, the protein in the same Mr region of the polyacrylamide gel reacted with adrenodoxin antibody and co-migrated with bovine adrenodoxin. PTH and forskolin treatment resulted in decreased phosphate incorporation into the protein, whereas A23187 treatment increased the phosphorylation. In parallel experiments, affinity-isolated hydroxylase from control and PTH-treated slices was used to assess in vitro hydroxylase activity using [3H]25-hydroxyvitamin D3 as substrate. The hydroxylase activity derived from PTH-treated tissue was significantly higher than that of control. From these data, it is proposed that renal response to PTH in terms of 25-hydroxyvitamin D3 hydroxylase stimulation involves dephosphorylation of renoredoxin, the ferrodoxin component of this hydroxylase complex.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1986

The developmental expression of the gene for TFIIIA in Xenopus laevis.

The sequence of the trans-acting positive transcription factor TFIIIA has been deduced by sequencing cDNA and genomic DNA clones. Using DNA from a homozygous diploid animal we show that there is one gene for TFIIIA per haploid genome of X. laevis. Protein sequencing of proteolytic fragments of TFIIIA orients the protein in its interaction with the internal control region (ICR) of the 5S RNA gene. The protein lies along the DNA with its carboxyl terminus at the 5' end of the ICR and its amino terminus at the 3' end. The developmental pattern of TFIIIA and its mRNA during oogenesis and embryogenesis are consistent with the idea that the abundance of TFIIIA plays an essential role in the developmental change in 5S RNA gene expression. The change to almost exclusive somatic 5S RNA gene expression by gastrulation occurs using either the TFIIIA that was synthesized by oocyte and/or TFIIIA synthesized from maternal mRNA.

Amino Acid Sequence↗
PubMed1985

Effect of treatment with cyclosporine versus azathioprine on incidence and severity of cytomegalovirus infection posttransplantation.

The incidence and severity of cytomegalovirus (CMV) infection were evaluated in 24 renal transplant patients treated with steroids and cyclosporine and compared with 40 patients treated with steroids and azathioprine: 58% of patients receiving azathioprine and 33% of patients receiving cyclosporine required additional therapy with antithymocyte globulin (ATG) to treat steroid-resistant rejections. CMV antibody titers and cultures of urine and saliva were determined monthly for 4-6 months following transplant in all patients. Both the frequency of CMV infection (occurring in 58% of patients on steroids and cyclosporine and in 48% of patients on steroids and azathioprine) and its severity (21% of cyclosporine-treated patients and 22% of azathioprine-treated patients with symptoms) were similar in both groups. Use of ATG was associated with an increased incidence of CMV disease, especially for patients in the azathioprine group. Both the incidence of CMV disease, and the number of patients with symptoms in the azathioprine group were significantly lower when patients who had received ATG were excluded from analysis. When results were analyzed in just the cadaveric recipients in each group, the incidence and severity of CMV infection tended to be higher in azathioprine-treated patients compared with those maintained on cyclosporine. This could have been explained by the more frequent use of ATG in 84% of azathioprine maintained patients compared with 35% of cyclosporine-treated patients (P less than 0.002) since other factors, such as risk for CMV infection and Solumedrol dose for rejection were similar in both groups. The data demonstrate that ATG has a deleterious influence on the incidence and severity of CMV infection in renal transplant patients, even when the dosage of other immunosuppressive drugs is decreased during ATG therapy. Since patients treated with steroids and azathioprine tend to require ATG to treat steroid-resistant rejection more frequently than do patients on cyclosporine, this effect of ATG must be taken into account when evaluating CMV infection in patients on these two drug regimens.

Azathioprine↗