rPF4 does not cause pulmonary hypertension in humans.
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Humans↗
Biomedical subjects
A Alexander
Publications and source records attributed to A Alexander.
The effect of dexamethasone, cyclosporine, and rapamycin on T-lymphocyte proliferation in vitro: comparison of cells from patients with glucocorticoid-sensitive and glucocorticoid-resistant chronic asthma.
Inhibition of T-lymphocyte activation may provide a useful approach to the treatment of chronic severe asthma. We compared rapamycin, a novel immunosuppressive drug, with cyclosporine and dexamethasone for its effects in inhibiting proliferation of T lymphocytes from patients with glucocorticoid-resistant and glucocorticoid-sensitive asthma. Phytohemagglutinin-stimulated peripheral blood T lymphocytes from 11 patients with clinically glucocorticoid-resistant and 8 patients with glucocorticoid-sensitive chronic asthma were tested for sensitivity to these drugs in a highly reproducible proliferation assay. All drugs inhibited proliferation in a dose-dependent manner (10(-6) to 10(-10) mol/L). T lymphocytes from the patients with glucocorticoid-resistant asthma were significantly less sensitive (p < 0.01) to dexamethasone than those of patients with glucocorticoid-sensitive asthma over a wide concentration range. In contrast, cyclosporine and rapamycin inhibited cells from both patient groups to an equivalent extent. The presence of exogenous interleukin-2 abrogated the inhibitory effect of dexamethasone but not that of cyclosporine or rapamycin, suggesting that dexamethasone may act principally by inhibition of interleukin-2 production, whereas the latter drugs exert distinct or additional inhibitory effects. Stimulation of peripheral blood T lymphocytes with phytohemagglutinin for 24 hours before addition of the drugs abolished the inhibitory effect of dexamethasone and significantly reduced that of cyclosporine. The inhibitory effect of rapamycin was, however, unaltered. These data suggest that dexamethasone and cyclosporine exert their effects only at an early stage of T-lymphocyte activation, whereas rapamycin is able to inhibit lymphoblasts. The fact that the inhibitory mechanisms of these drugs are different might explain why cyclosporine and rapamycin are effective in inhibiting T lymphocytes from both patients with glucocorticoid-sensitive and those with glucocorticoid-resistant asthma. The data further suggest that cyclosporine and rapamycin may be effective for the therapy of glucocorticoid-resistant asthma.
Adult↗
Distribution of the matrix metalloproteinases stromelysin, gelatinases A and B, and collagenase in Crohn's disease and normal intestine.
AIMS: To investigate the role of the matrix metalloproteinases (MMPs) in the connective tissue changes seen in the intestine in Crohn's disease. METHODS: Indirect immunofluorescence microscopy using specific antibodies to the MMPs (collagenase, gelatinase A and B, and stromelysin) were used to assess the distribution of these enzymes in normal and diseased intestine. RESULTS: In normal intestine the matrix metalloproteinases were confined to a few isolated inflammatory cells, but in Crohn's disease, the inflammatory infiltrate was associated with increased numbers of polymorphonuclear leucocytes which stained positive for gelatinase B. Stromelysin was also detected extracellularly on the connective tissue matrix in regions of smooth muscle cell proliferation and mucosal degradation. Interestingly, in ulcerative colitis, another inflammatory bowel disease, stromelysin was localised in the lamina propria in regions of mucosal loss. CONCLUSIONS: The increased numbers of inflammatory cells containing gelatinase B, and the localisation of extracellular stromelysin in regions of fibrosis and mucosal degradation, suggest that these enzymes have a role in the pathological changes seen in Crohn's disease. In cases of ulcerative colitis stromelysin was also detected on the lamina propria in regions of mucosal loss, and seems to be associated with the connective tissue changes that precede mucosal loss.
Colitis, Ulcerative↗
Toluene abuse: physical basis for hypointensity of the basal ganglia on T2-weighted MR images.
PURPOSE: To explain the hypointensity in the basal ganglia on T2-weighted magnetic resonance (MR) images of brains of toluene abusers. MATERIALS AND METHODS: Eight patients with histories of toluene abuse underwent MR imaging. A bilayered model of dipalmitoylphosphatidylcholine (DPPC; 100 mmol/L concentration) and varying concentrations of toluene was formed. The DPPC control and toluene-mixed bilayers underwent MR imaging. T1 and T2 were measured as a function of toluene and lipid concentrations. RESULTS: T2-weighted images of patients who had abused toluene showed marked hypointensity in the thalami and moderate hypointensity in the basal ganglia. Measurements of the DPPC-toluene phantom indicated that toluene-tainted lipid bilayers dramatically shortened T2 and had little effect on T1. By comparison, DPPC itself had little discernible effect on either T1 or T2. CONCLUSION: This model suggests that partitioning of toluene into the lipid membranes of cells in cerebral tissue may be responsible for the hypointensity of basal ganglia noted on T2-weighted MR images of brains of toluene abusers.
Adult↗
Effects of genotype and cryopreservation of avian semen on fertility and number of perivitelline spermatozoa.
1. The fertility of freshly diluted and cryopreserved samples of semen obtained from a population of chickens selected for duration of fertility of cryopreserved spermatozoa (FS line) and its unselected control (FC line) were compared over a range of spermatozoa concentrations (10, 40, 80, and 160 x 10(6) sperm/50 microliters insemination). 2. The spermatozoa of the FS line had greater fertility than spermatozoa of the FC line, whether freshly diluted or cryopreserved. Cryopreservation resulted in a reduction in fertility, regardless of line. There were no significant line by genotype interactions. 3. There were fewer spermatozoa from the FC line than the FS line found in the perivitelline membrane (perivitelline spermatozoa). The increase in number of perivitelline spermatozoa with increasing sperm concentration was greater in the FS than FC line. However, the slope of the increase in sperm number in the perivitelline membrane with increasing concentrations of cryopreserved spermatozoa was zero. 4. A minimum of 10(3) perivitelline spermatozoa must be found on day 2 post-insemination for duration of fertility to exceed three days. The ability to produce spermatozoa capable of reaching the forming perivitelline membrane appears to be a quantitative, rather than a qualitative, trait and may be subject to genetic manipulation.
Animals↗
Distribution of adenylate cyclase and GTP-binding proteins in hepatic plasma membranes.
Hepatic membrane subfractions prepared from control rats demonstrated forskolin (FSK)-stimulated adenylate cyclase activity in the basolateral (sinusoidal) but not apical (canalicular) plasma membrane. After bile duct ligation (BDL) for 12 or 24 h, there was an increase in FSK-stimulated adenylate cyclase activity in the apical membrane (54.2 +/- 3.9 pmol.mg-1 x min-1). The mechanism for this increase was explored further. ATP hydrolysis was found to be much higher in the apical than the basolateral membrane. Increasing the ATP levels in the assay enhanced apical membrane adenylate cyclase activity (10.5 +/- 0.2 pmol.mg-l.min-1); however, total adenosinetriphosphatase (ATPase) activity was not altered after BDL. Extraction of the apical membrane with bile acids or other detergents resulted in a two- to threefold increase in adenylate cyclase activity (30.6 +/- 3.6 pmol.mg-1 x min-1; detergent C12E8) This suggested that bile duct ligation was acting via the detergent-like action of bile acids to uncover latent adenylate cyclase activity on apical membranes. Further studies demonstrated that both BDL and detergent extraction also enhanced toxin-directed ADP-ribosylation of Gs alpha (cholera toxin) and Gi alpha (pertussis toxin) in the apical but not the basolateral membrane. After BDL, Gi alpha was found to be twofold greater in the apical membrane than the basolateral membrane. Immunoblotting using specific G protein antibodies further confirmed that apical membranes from control rats had a higher concentration of Gi1, 2 alpha and beta and slightly elevated levels of Gi3 alpha and Gs alpha compared with the basolateral membrane. The results demonstrate that adenylate cyclase and heterotrimeric GTP-binding proteins are present on the apical membrane, but measurement of their functional activity requires detergent permeabilization of apical membrane vesicles and is limited by the presence of high ATPase activity.
Adenosine Triphosphatases↗
Requirement for three membrane-spanning alpha-helices in the post-translational insertion of a thylakoid membrane protein.
The insertion of a protein into a lipid bilayer usually involves a short signal sequence and can occur either during or after translation. A light-harvesting chlorophyll a/b-binding protein (LHCP) is synthesized in the cytoplasm of plant cells as a precursor and is post-translationally imported into chloroplasts where it subsequently inserts into the thylakoid membrane. Only mature LHCP is required for insertion into the thylakoid. To define which sequences of the mature protein are necessary and sufficient for thylakoid integration, fusion and deletion proteins and proteins with internal rearrangements were synthesized and incubated with isolated thylakoids and stroma. No evidence is found for the existence of a short signal sequence within LHCP, and, with the exception of the amino terminus and a short lumenal loop, the entire mature protein with consecutively ordered alpha-helices is required for insertion into thylakoid membranes. The addition of positive charges into stromal but not lumenal segments permits the insertion of mutant LHCPs into isolated thylakoids. Replacement of the LHCP transit peptide with the transit peptide from plastocyanin has no effect on LHCP insertion and does not restore insertion of the lumenal charge addition mutants.
Base Sequence↗
Fine-needle aspiration of a periurethral Teflon-filled cyst following radical prostatectomy.
Periurethral Teflon injections are being used increasingly for the treatment of urinary incontinence after radical prostatectomy. We report a case of a man who developed increasing obstructive urinary symptoms and stress incontinence following radical retropubic prostatectomy. Six months earlier, he had undergone periurethral Teflon injections. On transrectal ultrasound and magnetic resonance imaging, a 3.2-cm cystic lesion was noted at the prostatic bed near the bladder neck where the Teflon had been injected. Ultrasound-guided transperineal fine-needle aspiration of the cyst yielded a specimen with numerous birefringent crystalline Teflon particles. Although previous reports have described granulomatous tissue reaction, no multinucleated giant cells were present to suggest granuloma formation. To our knowledge, this is the first reported case of Teflon cyst formation following periurethral Teflon injections. The patient's history, imaging studies, cytopathology, and review of the literature are presented in this report.
Aged↗
Arthroscopic surgery of the knee: its role in the support of U.S. troops during Operation Desert Shield on USNS mercy.
The role of arthroscopy in the preconflict deployment of a large number of military troops is not well defined. Between September 1990 and January 1991, while deployed to the Persian Gulf for Operation Desert Shield 73 patients underwent on-board elective arthroscopy on the USNS Mercy. There were 71 men and two women with an average age of 27 years (range 19-47). Indications for arthroscopy included clinical diagnosis of meniscus tear, acute hemarthrosis, chronic effusion, and intra-articular loose body. Findings at the time of arthroscopy included 34 patients (47%) with meniscus tears; 17 (23%) with anterior cruciate ligament tears; five (7%) with isolated grade II-IV chondromalacia involving the patella, trochlea, femoral condyles, or tibial plateaus; six (8%) with synovitis; four (5%) with osteochondritis dissecans of the medial femoral condyle; two (3%) with a medial retinacular tear secondary to patella dislocation; and 10 (14%) with normal arthroscopic examinations. Forty-nine patients (66%) were returned to duty at an average of 6 days postoperatively, obviating the need to evacuate these patients from the Middle East theatre.
Adult↗
Treatment of iatrogenic femoral artery injuries with ultrasound-guided compression.
Iatrogenic injuries of the groin are becoming more common after increasingly sophisticated vascular intervention. These injuries are accurately detected by duplex and color Doppler ultrasonography. Recent treatment of these lesions by ultrasound-guided compression repair (UGCR) has been described. During a 1-year period we identified 18 femoral artery injuries, including 17 pseudoaneurysms and one arteriovenous fistula. Three of the pseudoaneurysms thrombosed spontaneously before attempted treatment. The remaining 15 lesions underwent a trial of UGCR. Successful closure was accomplished in 10 patients (56%). Seven of these lesions were successfully treated during the initial session, and thrombosis was accomplished after repeat compression in three additional lesions. Three patients who were given anticoagulants had a failed UGCR, but their pseudoaneurysms thrombosed after administration of anticoagulants was discontinued. Two patients had failed UGCR and required operation. Seven (88%) of eight patients who were not given anticoagulants were successfully treated. In contrast only two (29%) of seven patients given therapeutic doses of anticoagulant medication were successfully treated by the technique. There was no statistical difference between mean pseudoaneurysm diameter, mean width and length of pseudoaneurysm neck, or depth of pseudoaneurysm neck from skin surface in patients in whom successful initial closure was achieved when compared with those patients in whom the initial attempt failed. UGCR is a safe, simple, noninvasive technique that can be used to treat many femoral artery injuries that traditionally were treated with surgery. The technique can be applied by any laboratory that has the necessary ultrasonography equipment and is currently the method of choice for treating uncomplicated iatrogenic femoral artery injuries at our institution.
Adult↗
Ablation of osteoid osteomas with a percutaneously placed electrode: a new procedure.
Osteoid osteoma is a benign, self-limited tumor of bone that usually requires surgical excision for relief of pain and to prevent long-term consequences. Radio-frequency electrodes have been successfully and safely used to ablate small areas of the central nervous system and to perform ablation elsewhere in the body. The authors have used this technique in four patients with proved or presumptive osteoid osteoma, completely relieving the symptoms in three.
Adult↗
Endoluminal sonography of the urinary tract: preliminary observations.
Endoluminal sonography of the urinary tract was performed by using endoluminal ultrasound transducers contained within 2-mm-diameter catheters. The catheters were inserted into the urinary bladder via the urethra and advanced into the ureters and renal pelvis under cystoscopic control; then, cross-sectional images of the bladder, ureters, and renal pelvis were obtained. Two dogs and seven human patients were studied. In one dog, a 4.5-mm pseudopolyp, which was surgically created in the bladder wall, was successfully imaged; in the other, stones 2 mm or larger inserted into the bladder were identified. Of the seven patients, sonography showed stones embedded in the renal parenchyma (one patient) and the mucosa of the distal ureter (one patient). These were ultimately confirmed by their eventual removal. In a third, sonography showed a tumor of the distal ureter and identified the depth of the tumor. This was confirmed by biopsy. In a fourth, sonography clearly showed a crossing vessel as the cause for narrowing of the proximal ureter. In a fifth, sonography showed that the cause of a ureteral stricture was idiopathic. In the last two cases, sonography did not reveal a cause for hematuria. In these last three cases, negative sonographic results were confirmed by direct ureteroscopic examinations and follow-up studies. Our observations based on this limited study suggest that endoluminal sonography is a useful procedure for diagnosing diseases of the urinary tract. Further study is warranted.
Adult↗
Net production of cerebrospinal fluid is decreased by SCH-23390.
A high density of binding sites for the ligands 3H-SCH-23390 and 3H-SKF-83566 has been found in the choroid plexus. Although these sites have similar pharmacology to D1 dopamine receptors, the high-affinity component of 3H-SCH-23390 binding in the choroid plexus has been identified as the 5-HT1c subtype of serotonin receptor. We investigated the possible role of these receptors in modulating the production of cerebrospinal fluid (CSF) in rats. (R) SCH-23390 produced up to a 50% decrease in net CSF production, compared to saline. This compound is a partial agonist at 5-HT1c serotonin receptors, and an antagonist at D1 dopamine receptors. The (S) enantiomer of SCH-23390 (SCH-23388) was ineffective. Drugs interacting with receptors for neurotransmitters in the choroid plexus may hold promise for the treatment of patients with increased intracranial pressure, including those with mass lesions, head trauma, acute or chronic hydrocephalus, or pseudotumor cerebri.
Animals↗
Metalloproteinases in the intestine of patients with Crohn's disease.
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Crohn Disease↗
Supplies. The nurse's role in the efficient management of resources.
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Equipment and Supplies, Hospital↗
Biotinylated RNA probes for the detection of potato spindle tuber viroid (PSTV) in plants.
Diseases caused by potato spindle tuber viroid (PSTV) are of significant agronomic importance, and early detection is vital. The objective of this paper was to synthesize biotinylated RNA probes in order to develop a specific, sensitive, and reliable assay system for detection of PSTV in infected plants. RNA probes were prepared by in vitro transcription of cloned PSTV, and were labelled with either biotin-11-UTP or [32P]UTP. Partially purified total RNAs from healthy and from PSTV-infected plants were spotted onto nitrocellulose filters and hybridized with either biotin-labelled or 32P-labelled probes. Our results showed that the sensitivity of biotinylated probes was similar to that for the 32P-labelled probes.
Biotin↗
Role of glutamic acid 177 of the ricin toxin A chain in enzymatic inactivation of ribosomes.
The gene for the A chain of ricin toxin was fused to a beta-galactosidase marker cistron via a DNA sequence encoding a short collagen linker, and the tripartite fusion protein was expressed in Escherichia coli. Site-specific mutagenesis was used to change glutamic acid residue 177 to aspartic acid or alanine. When the mutant proteins were expressed, purified, and tested quantitatively for enzymatic activity, the carboxylate function at position 177 was found not to be absolutely essential for ricin toxin A-chain catalysis.
Blotting, Western↗
Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.
A genomic clone was isolated from a human lymphoid cell line which synthesized an NH2-terminally deleted gamma 3 heavy chain disease protein. Nucleotide sequence analysis revealed a normal sequence from 310 bp 5' to the initiator ATG through the codon for VH amino acid 14. Amino acid 15 was derived from the codon for the last J4 amino acid. Thus, the clone contained a deletion of the codons for the VH region beyond amino acid 14, as well as those for the entire D region and most of the J coding region. Some sequence abnormalities were observed in the 400 bp after the deletion. Beyond this, there was excellent homology to published J and intervening sequences, including those containing the enhancer elements. The 1,200-bp switch region was abruptly interrupted by a sequence corresponding to the 3' one-third of CH1. Thus, a second deletion eliminated the acceptor splice site at the 5' end of CH1. When splicing of the primary RNA transcript occurred, the truncated VH region was joined via the J4 donor splice site to the next available acceptor site 5' to the first hinge exon. Hence, the aberrant serum protein was the product of two deletions and a splice correction as well as postsynthetic NH2-terminal proteolysis.
Amino Acid Sequence↗