Search PubMed⌕ Search

Biomedical subjects

S Collins

Publications and source records attributed to S Collins.

At least 217 records · Page 12Linked to original sources

Lymphomatoid granulomatosis presenting as a progressive cervical cord lesion.

A 50-year-old male presented with symptoms of a progressive spinal cord lesion over two and a half months investigations, including myelography, CT scan and magnetic resonance imaging (MRI), did not show cord compression although the MRI scan demonstrated thickening of the posterior cervical meninges. CSF examination revealed pleocytosis, increased total protein and cells suggestive of a lymphoproliferative disorder. Open lung biopsy of an asymptomatic left midzone mass was diagnostic of lymphomatoid granulomatosis. We believe this to be a case of lymphomatoid granulomatosis presenting as a progressive cervical myelopathy.

Diagnosis, Differential↗

Genetic regulation of beta-adrenergic receptors.

Several members of the family of receptors coupled to G proteins have been cloned in recent years. From the primary sequence information furnished by these clones, a characteristic seven-membrane spanning topography has emerged as the prototype for this class of receptors, in analogy with the opsin visual pigments. Cloned genes for the various receptors provide important tools for probing the regulation of their expression. For example, the underlying genetic basis for the expression of adrenergic receptor subtypes can now be explored. The physiological regulation of receptors by heterologous hormones, such as steroids and thyroid hormones, has long been suspected to involve changes in the expression of the relevant adrenergic receptor genes. At least for the glucocorticoids, beta 2AR expression is controlled at the level of transcription. The hormonal regulation of other adrenergic receptor subtypes is currently being explored.

Animals↗

Decreased dehydroepiandrosterone sulfate in pigmented nodular adrenal dysplasia.

Previous reports on patients with endogenous Cushing's syndrome describe low concentrations of the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) in adrenal adenoma and in a case of feminizing macronodular hyperplasia. Here we present hormonal data from two adult sisters with Cushing's syndrome as a result of pigmented nodular adrenal dysplasia. Corticotropin concentrations were in the mid-normal range, cortisol production was unaffected by administration of dexamethasone (8 mg/24 h), and baseline concentrations of DHEA-S were less than 0.5 mumol/L. A low concentration of DHEA-S in these and other previously reported patients with Cushing's syndrome correctly predicts the results of dynamic testing. Decreased DHEA-S in a patient with endogenous Cushing's syndrome can be ascertained by assay of a single sample and should prompt consideration of the diagnosis of autonomous bilateral nodular disease as well as adrenal adenoma.

Adrenal Glands↗

A rapid screening method for routine female genital tract swabs.

Many hospital laboratories process large numbers of female genital tract swabs to confirm or eliminate the common causes of vaginal discharge. Employing media for culture and acridine orange fluorescent stain for microscopy provides a sensitive, economic and time saving method for routine screening of these types of specimen.

Acridine Orange↗

Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids.

Steroid hormones modulate adrenergic receptor responsiveness and receptor number. To investigate the regulation of the beta 2-adrenergic receptor gene by glucocorticoids we examined the effects of the synthetic glucocorticoid agonist triamcinolone acetonide on the expression of beta 2-adrenergic receptors in DDT1MF-2 hamster smooth muscle cells. Glucocorticoid treatment (1 X 10(-7) M) produced a 2.2 +/- 0.4-fold (n = 8) increase in beta 2-adrenergic receptor number (maximum) between 6 and 12 h) as determined by radioligand binding and a similar increase in catecholamine-stimulated adenylate cyclase activity. Steady-state levels of beta 2-adrenergic receptor mRNA, analyzed by Northern blot hybridization, were increased 2.4 +/- 0.4-fold (n = 6) within 1 h, while actin mRNA levels were unchanged throughout the experiment. These steroid-induced increases in beta 2-adrenergic receptor mRNA returned to control levels by 24 h and were followed by a much slower decline in beta 2-adrenergic receptor in plasma membranes. The rate of beta 2-adrenergic receptor gene transcription, assessed by nuclear run-off transcription assays, increased 3.1 +/- 0.1-fold (n = 2) in cells treated for 30 min with 1 X 10(-7) M triamcinolone acetonide. These studies indicate that glucocorticoids regulate the beta 2-adrenergic receptor-adenylate cyclase system by controlling the rate of transcription of the beta 2-adrenergic receptor gene and hence the responsiveness of the enzyme to catecholamine stimulation.

Adenylyl Cyclases↗

Regulation of the beta 2-adrenergic receptor and its mRNA in the rat ventral prostate by testosterone.

To investigate the regulation of beta 2AR expression in rat ventral prostate the effects of castration and testosterone replacement on the beta 2AR were studied by ligand binding and Northern blot analysis. Orchidectomy depressed beta 2AR number by 50% within 4 days and testosterone administration to 4-day castrates produced a rapid and complete recovery of beta 2AR number within 24 h. In contrast to receptor number, beta 2AR mRNA levels did not change relative to total RNA following castration. However, during the testosterone replacement period beta 2AR mRNA levels rose transiently, reaching a maximum (3.5-fold) between 8 and 12 h, and this increase in mRNA preceded the recovery in beta 2AR number in the membrane. Regulation of beta 2AR gene expression by testosterone in the ventral prostate is thus complex and probably involves both transcriptional and post-transcriptional components.

Animals↗

The effect of coronary angioplasty on coronary flow reserve.

To determine the effects of coronary angioplasty on coronary flow reserve (CFR), we studied 32 patients before and immediately after single-vessel coronary angioplasty and 31 patients evaluated late after angioplasty (7.5 +/- 1.2 months, mean +/- SEM). The geometry (percent area stenosis and minimal cross-sectional area) of each lesion was determined by quantitative coronary angiography (Brown/Dodge method) and the integrated optical density was measured by videodensitometry. CFR was measured with a No. 3F coronary Doppler catheter placed immediately proximal to the lesion and a maximally vasodilating dose of intracoronary papaverine. The translesional pressure gradient was obtained in all lesions before and immediately after angioplasty and in 18 of 31 vessels late after angioplasty. CFR immediately after angioplasty returned to normal levels (greater than 3.5 peak/resting velocity ratio) in 14 of 31 patients and was improved, although not normalized, in the remaining 17 patients. CFR immediately after dilation was not significantly correlated with any of the angiographic variables of arterial stenosis nor the resting pressure gradient. Moreover, the pressure gradient and absolute distal coronary pressure at peak hyperemia were not significantly different in vessels with normal and those with abnormal flow reserve immediately after dilation, suggesting that the residual stenosis did not significantly limit hyperemia. Late after angioplasty, however, a significant relationship emerged between CFR and all four indexes of residual arterial stenosis (percent area stenosis r = .70, p less than .01; minimum arterial cross-sectional area r = .70, p less than .01; integrated optical density r = .60, p less than .01; and translesional pressure gradient r = .77, p less than .01). Furthermore, in the absence of restenosis, CFR eventually normalized in all patients. These findings demonstrate that in one-half of patients there is a transient reduction in coronary flow reserve immediately after angioplasty. In the absence of restenosis, coronary flow reserve later normalizes. Consequently, measurements of coronary flow reserve immediately after angioplasty may not reflect the eventual success of the procedure in removing physiologic obstruction to coronary blood flow.

Angiography↗

Expression of a human cDNA encoding the beta 2-adrenergic receptor in Chinese hamster fibroblasts (CHW): functionality and regulation of the expressed receptors.

A human beta-adrenergic receptor cDNA was transfected and expressed in transformed Chinese hamster fibroblasts (CHW). The expressed receptor exhibited a typical beta 2-adrenergic selectivity for agonists and antagonists as assessed by radioligand binding and adenylate cyclase activation. Guanine nucleotide-sensitive high affinity binding of the agonist, isoproterenol, indicated effective coupling of the expressed receptor to a guanine nucleotide-regulatory protein. The level of expression of beta 2-AR in various cell clones varied over 200-fold and was positively correlated with the levels of beta 2-AR mRNA. In cells expressing between 0.04 and 3.0 pmol of beta 2-AR/mg of membrane protein, the efficacy of isoproterenol for stimulating adenylate cyclase increased with increasing numbers of expressed receptors but reached a plateau and started to decrease in clones with higher beta 2-AR density (3.0-8.0 pmol/mg of membrane protein). Preincubation of beta 2-AR-expressing cells with isoproterenol for 15 min led to significant reduction in the level of isoproterenol-sensitive adenylate cyclase activity. This agonist-induced desensitization was also accompanied by phosphorylation of the beta 2-AR. These data indicate that the expressed human beta 2-AR displays typical functional characteristics of adenylate cyclase-coupled receptors including agonist-induced desensitization. Moreover, the availability of this series of cellular clones, which differ markedly in their density of beta 2-AR, provides a unique set of biological reagents for future studies of beta 2-AR function and regulation.

Adenylyl Cyclases↗

A prospective study of the predictive value of electroencephalographic abnormalities for epileptic loss of consciousness.

Patients referred to a neurology clinic with their first episode of loss of consciousness were studied prospectively in order to clarify the positive predictive value of an epileptic EEG for establishing an epileptic cause of the loss of consciousness. The clinical diagnosis was categorised as epileptic or non-epileptic. The EEG was reported as epileptic or non-epileptic, but abnormal or normal, according to recognised criteria. Patients were followed for a period ranging from 1 to 18 months to assess the accuracy of the original diagnosis. A total of 38 patients were available for analysis. Thirteen patients had a clinical diagnosis of epilepsy and 25 patients had a non-epileptic diagnosis. Five patients with an epileptic history had an epileptic EEG and 2 patients with a non-epileptic history had an epileptic EEG. Non-epileptic EEG abnormalities were present in a further 4 patients with a non-epileptic history. Follow-up was achieved for 53% of patients and in none of these was the final diagnosis different from the initial one. The positive predictive value of an epileptic EEG for a diagnosis of epilepsy was 71%, and the negative predictive value of a normal EEG for a diagnosis of non-epilepsy was 74%. The positive predictive value for any abnormality in the EEG for a diagnosis of epilepsy was 45%, and the negative predictive value of an absence of any abnormality in the EEG for a diagnosis of non-epilepsy was 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A family with late onset autosomal dominant cerebellar degeneration.

A family is described in which 5 (4 female and 1 male) of 8 siblings from one marriage developed a late onset cerebellar degeneration. Four of the 5 affected persons presented separately to different neurologists. Because the original enquiries into family history were negative, and because of the exclusion of other recognised causes for the clinical picture, a diagnosis of idiopathic chronic cerebellar degeneration was made for the individual patients. All patients experienced their first symptoms between the ages of 48 and 55 years, with a gradual unremitting deterioration from the onset. Cerebellar atrophy was confirmed on CT head scan in all cases. Clinically, apart from the cerebellar ataxia, there were no consistent signs of degeneration of any other central or peripheral nervous system pathway. Geographical factors severely limited family contact, and consequently none of those afflicted was aware of similarly affected relatives. Hence, this particular family illustrates the great importance of obtaining a detailed, accurate family history and of assiduous follow-up of the entire family. Only after many years did it become obvious that multiple members of the family were affected by a similar neurological problem.

Aged↗

Intramedullary spinal cord metastasis in Hodgkin's disease. Rapid diagnosis and treatment resulting in neurologic recovery.

Intramedullary spinal cord metastases are uncommon in Hodgkin's disease and have a poor prognosis. This prognosis reflects the refractory or widely disseminated status of the disease at the time of development of neurological symptoms and difficulties in diagnosis. Computerized tomography and magnetic resonance imaging have enabled more rapid and specific diagnosis of spinal cord diseases. The authors report a patient who presented with Brown-Sequard syndrome due to intramedullary spinal cord infiltration from Hodgkin's disease. This patient was diagnosed promptly and with rapid initiation of radiation and chemotherapy, she has had neurologic recovery.

Adult↗

Cloning of the cDNA for the human beta 1-adrenergic receptor.

Screening of a human placenta lambda gt11 library has led to the isolation of the cDNA for the human beta 1-adrenergic receptor (beta 1AR). Used as the probe was the human genomic clone termed G-21. This clone, which contains an intronless gene for a putative receptor, was previously isolated by virtue of its cross hybridization with the human beta 2-adrenergic receptor (beta 2AR). The 2.4-kilobase cDNA for the human beta 1AR encodes a protein of 477 amino acid residues that is 69% homologous with the avian beta AR but only 54% homologous with the human beta 2AR. This suggests that the avian gene encoding beta AR and the human gene encoding beta 1AR evolved from a common ancestral gene. RNA blot analysis indicates a message of 2.5 kilobases in rat tissues, with a pattern of tissue distribution consistent with beta 1AR binding. This pattern is quite distinct from the pattern obtained when the beta 2AR cDNA is used as a probe. Expression of receptor protein in Xenopus laevis oocytes conveys adenylate cyclase responsiveness to catecholamines with a typical beta 1AR specificity. This contrasts with the typical beta 2 subtype specificity observed when the human beta 2AR cDNA is expressed in this system. Mammalian beta 1AR and beta 2AR are thus products of distinct genes, both of which are apparently related to the putative G-21 receptor.

Amino Acid Sequence↗

Expression of bcr and bcr-abl fusion transcripts in normal and leukemic cells.

The translocation of the c-abl oncogene from chromosome 9 to the bcr gene on chromosome 22 in cases of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) generates an aberrant bcr-abl fusion transcript which may be intimately related to the pathogenesis of CML. Because factors controlling normal bcr expression might also be involved in the expression of this aberrant bcr-abl transcript, we studied the patterns of expression of the normal bcr gene in different cell types. We found that the normal bcr gene was expressed in many different types of human cells. Moreover, the bcr gene was evolutionarily conserved, and homologous bcr genomic sequences and RNA transcripts were readily detected in chick tissue. The highest level of bcr expression in chick tissue was in brain tissue, the lowest level was in liver tissue, and a truncated bcr mRNA was noted in chick testes. Normal bcr transcripts, in addition to the aberrant bcr-abl hybrid transcripts, have been found in all Philadelphia chromosome-positive CML cells studied to date. Within a given CML sample, the relative amounts of normal bcr RNA and aberrant bcr-abl RNA were similar. In addition, the normal bcr and the aberrant bcr-abl hybrid transcripts demonstrated similarly prolonged half-lives compared with that of the normal abl-related transcripts in CML cells. These findings suggest that in CML cells, similar cellular mechanisms control the steady-state levels of both the normal bcr and the bcr-abl fusion RNAs.

Cell Line↗

Constitutive and inducible secretion of platelet-derived growth factor analogs by human leukemic cell lines coexpressing erythroid and megakaryocytic markers.

We have examined the constitutive and inducible secretion of platelet-derived growth factor (PDGF)-like proteins in a variety of human hemopoietic cell lines. The highest levels of secreted protein were noted in four human erythroleukemia lines which, in addition to erythroid lineage markers, express one or more megakaryocytic lineage markers. Induction of these lines by 12-O-tetradecanoylphorbol-13-acetate enhanced the expression of megakaryocytic markers and increased secretion of PDGF-like proteins several fold. In concert with these changes, there was significant induction of c-sis/PDGF-B messenger RNA (mRNA) expression in all lines, whereas one line showed significant concurrent induction of PDGF-A mRNA expression. Whether PDGF-like secretion is part of the stem cell-like phenotype displayed by these lines or is secondary to their leukemic transformation remains to be determined. Nevertheless, these lines provide new cellular models for studying the expression and function of PDGF analogs in hemopoietic cells.

Cell Differentiation↗

Purification of a benzo[a]pyrene binding protein by affinity chromatography and photoaffinity labeling.

Binding proteins for the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) have been purified from C57B1/6J mouse liver. Following affinity chromatography on aminopyrene-Sepharose, a single polypeptide of 29,000 daltons was isolated. The photolabile compound 1-azidopyrene was developed as a photoaffinity labeling agent to identify the protein during its purification. 1-Azidopyrene was found to be a competitive inhibitor of [3H]B[a]P binding. Affinity labeling studies with [3H]-1-azidopyrene in unfractionated cytosol, and in purified preparations, yielded a single covalently labeled protein of 29,000 daltons. The formation of this labeled species was blocked by preincubation with excess unlabeled B[a]P. A native molecular weight of 30,000 was estimated by gel filtration chromatography of [3H]B[a]P- and [3H]-1-azidopyrene-labeled cytosol proteins. An equilibrium dissociation constant of 2.69 +/- 0.66 nM and a maximum number of binding sites of 2.07 +/- 0.10 nmol of [3H]B[a]P bound/mg of protein were estimated for the pure protein. Two-dimensional gel electrophoresis further resolved the purified 29,000-dalton protein into three major isoelectric variants, each of which was specifically labeled by [3H]-1-azidopyrene.

Affinity Labels↗

Plasmapheresis: an adjunct to medical management of severe hyperthyroidism.

A woman with hyperthyroidism and myasthenia gravis developed respiratory failure in association with radiation-induced thyroiditis. Treatment with steroids, propylthiouracil, propranolol, iodine, and plasmapheresis was associated with dramatic reduction in serum triiodothyronine (T3), serum thyroxine (T4), and thyroglobulin levels and prompt recovery of the patient. The medications that this patient received have been shown to cause an abrupt decline in serum T3 levels with little or no effect on the serum T4 concentration. The 56% decline in serum T4 observed in this patient during the first 24 hours of therapy suggests that plasmapheresis may be a useful adjunct to medical therapy in selected patients with severe hyperthyroidism.

Adult↗

Development of an affinity chromatography resin for the purification of carcinogen binding proteins from mouse liver.

Pyrene, a structural analog of benzo[a]pyrene, is an effective competing ligand for high affinity carcinogen binding proteins in mouse liver. A pyrene-derivatized Sepharose gel was prepared for affinity chromatography purification of these proteins, and adsorbs all detectable [3H]B[a]P-binding activity from hepatic cytosol with the adsorption of less than 1% of total protein. Specific carcinogen binding activity is recovered from pyrene-derivatized Sepharose columns with the enrichment of a 33 kDa polypeptide. This chromatography resin represents a major step in the isolation of these unusual receptor-like binding proteins for aromatic hydrocarbon carcinogens.

Animals↗