Exercise intolerance and ankle edema in a young woman.
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Adult↗
Biomedical subjects
C A Koch
Publications and source records attributed to C A Koch.
Cushing's syndrome in childhood and adolescence.
OBJECTIVE: To review the diagnosis, management and outcome of Cushing's syndrome in children and adolescents. METHODS: We conducted a retrospective review of nine cases treated between 1976 and 1996 at the Royal Children's Hospital, Melbourne, Australia. RESULTS: Six children with Cushing's disease and three with primary adrenal disease were identified. Mean age at diagnosis in the Cushing's disease patients was 11.3 years and in the children with primary adrenal disease 9.5 years. The most common presenting symptoms were weight gain and delayed growth. Two children had the unusual presenting symptoms of an eating disorder and hemihypertrophy, respectively. Laboratory diagnosis of Cushing's syndrome was established by demonstration of elevated urine free cortisol, loss of normal diurnal variation of serum cortisol, and loss of suppressibility of cortisol secretion by low dose dexamethasone. Investigations used to determine the aetiology of hypercortisolism included serum adrenocorticotropic hormone (ACTH) levels, high dose dexamethasone suppression tests, imaging studies, and inferior petrosal sinus sampling. Four patients with Cushing's disease had successful transphenoidal adenomectomies. Two patients with bilateral primary pigmented nodular adrenocortical dysplasia underwent bilateral adrenalectomies. One child with an adrenal adenoma was treated by left adrenalectomy. CONCLUSIONS: Cushing's syndrome in children and adolescents remains a diagnostic challenge. Successful treatment often requires the use of multiple tests to achieve the correct diagnosis, appropriate surgery and a good long-term outcome.
Adenoma↗
External leg compression in the treatment of vascular disease.
In summary, external compression of the limbs is a mode of therapy that has enjoyed a long history in the treatment of venous and arterial disease. Evidence suggests that its beneficial effects are mediated through enhancement of venous and arterial blood flow, promotion of vasodilation, enhancement of fibrinolysis, and, in the case of obstructive arterial disease, promotion of the development of collateral circulation. The utility of external leg compression in the prevention of deep venous thrombosis and in the management of chronic venous stasis disease has been well documented, and it has become an accepted treatment for these disorders. The use of pneumatic compression in the treatment of atherosclerotic peripheral vascular and cardiovascular disease is less widespread and its indications are less well defined. Though the work of a few investigators in each of these areas shows striking benefits of the technique, further investigation in these areas is warranted. Potential benefits to patients of external limb compression therapy include its non-invasive nature, its ability to be applied in an out-patient setting, and long-term cost savings through possible avoidance of hospitalization and invasive procedures.
Blood Circulation↗
Chicken joint amyloid protein is of the AA-type. I. Characterization of the amyloid protein.
Amyloid fibrils were extracted from deposits in joint tissue of heavy breed layers with spontaneous amyloid arthropathy and characterized as being of the AA-type. Amino acid sequencing revealed a pattern quite similar to duck AA. Acute phase sera of chicken experimentally injected with Enterococcus faecalis showed a SAA-protein like band cross reacting with anti-chicken AA in immunoblot.
Acrylic Resins↗
Exposure to domestic cats: risk factor for Pasteurella multocida peritonitis in liver cirrhosis?
Pasteurella multocida is most commonly associated with acute skin and soft tissue infections following an animal bite or scratch. Peritonitis caused by P. multocida in patients with cirrhosis is rarely reported. We present a case of spontaneous bacterial peritonitis with P. multocida in a patient with cirrhosis, squamous cell cancer of the head and neck, and nontraumatic domestic cat exposure. Nasopharyngeal colonization with P. multocida, with subsequent transient bacteremia and seeding of the peritoneum in immunocompromised (particularly cirrhotic) cat-owners, could play an important pathogenetic role in the development of spontaneous bacterial peritonitis. A review of the literature showed that in nine of 13 patients with cirrhosis and P. multocida peritonitis, exposure to domestic animals was reported. The mortality rate is high in this setting, even with prompt antibiotic treatment. Preventive strategies for immuno-compromised patients should include minimization of animal contact, especially cats, which have a high carriage rate (70-90%) of P. multocida.
Aged↗
Bullous pemphigoid after treatment with furosemide.
Bullous pemphigoid (BP) is a subepidermal blistering disease of the skin. Direct immunofluorescence is critical in establishing the diagnosis. Certain drugs are risk factors for the induction of BP. The association between BP and furosemide is rarely reported and has been challenged by a recent study. We describe a patient with BP after the administration of intravenous furosemide and review the literature on this topic. Drug-induced BP should be considered in patients who show bullous lesions shortly after administration of certain medications, with furosemide being a possible inciter.
Aged↗
Arachnoid cysts: does surgery improve epileptic seizures and headaches?
During the period from 1985 to 1992 we treated 43 patients with intracranial arachnoid cysts (ACs). In this retrospective study we assessed the outcome of these patients with regard to non-specific symptoms such as headaches and epileptic seizures. Twelve patients had headaches of obscure origin and a mostly temporal located AC. Six of these 12 underwent surgery. After the operation 4 patients (4/6) had no further headaches, two remained unchanged. The other 6 conservatively treated patients (6/12) had further headaches. Ten of the 43 patients had epileptic seizures. One patient dropped out of the survey. Six of the 9 remaining patients had a temporal AC. Four of these 6 underwent surgery; postoperatively the seizure disease of 3 patients (3/6) declined. One patient was unchanged. Two patients with epileptic seizures and a temporal AC did not undergo surgery and both improved. Three patients with seizures had a convex located AC. Two of these 3 underwent surgery. The first patient improved postoperatively, the second patient remained unchanged. There was a reduction in the seizures of the medically treated patient. It remains ambiguous, whether there is a relationship between epileptic seizures and intracranial ACs without obvious intracranial pressure signs. A review of the literature, however, showed mostly positive results concerning the surgical treatment of ACs under conditions of simultaneous epileptic seizures. However, the results largely depend upon the definition of the decline of the seizures with regard to the postoperative follow-up, therefore we must remain skeptical. Therapy guidelines in the future not only depend on the clarification of the pathophysiology of the ACs, but also on a resonable outcome examination.
Adolescent↗
Direct in vivo visualization of right cardiac anatomy by fiberoptic endoscopy. Hemodynamic effects and image validation.
The authors tested the ability of a balloon-tipped fiberoptic endoscope to accurately visualize and identify right-heart anatomy in 7 anesthetized dogs. A 3.6-mm-diameter fiberoptic endoscope with a latex balloon covering the distal tip was inserted into the right atrium, where the balloon was inflated with air in 5 mL increments. Heart rate did not show changes. Mean arterial pressure and cardiac output started to show significant decreases with a balloon volume at 25 and 20 mL, respectively (n = 7). Visual image quality was excellent with a balloon volume of 10 mL or greater. With a balloon volume of 7-10 mL, the visual field was 15-20 mm in diameter. Right-heart anatomy including the right free wall, ostium of the coronary sinus, atrioventricular node area, tricuspid valve, right ventricular structures, and pulmonary arteries was clearly and accurately identified. Additionally, spatial relationships among these structures could be established. Furthermore, there was an excellent concordance between endoscopically observed images and postmortem findings. In conclusion, balloon-tipped fiberoptic endoscopy can accurately visualize normal intracardiac structures with no or minimal hemodynamic compromise.
Animals↗
In vivo angioscopic visualization of right heart structure in dogs by means of a balloon-tipped fiberoptic endoscope: potential role in percutaneous ablative procedures.
We designed an angioscopic system that consisted of a fiberoptic endoscope enclosed in a polyurethane thin-wall tube with a latex balloon attached to its distal end. In 10 anesthetized closed-chest dogs the angioscope was placed in the right heart via a femoral vein. By inflating the balloon with 5 to 10 ml of normal saline solution to displace the blood, the endocardial structure of the right heart was visualized. Under fluoroscopic guidance and direct vision, an ablation catheter was placed inside the coronary sinus or in its vicinity, and radiofrequency energy was delivered through the catheter tip to create a lesion. The appearance and anatomic location of the lesion and the endocardial structure as seen through the angioscope correlated well with the results of postmortem examination. There were no or minimal changes in heart rate, blood pressure, or cardiac output by inflating the balloon to a volume of 15 ml in the right atrium or right ventricular cavity. An inflated balloon may produce single or repetitive atrial or ventricular arrhythmias, but not sustained tachyarrhythmia. Our study demonstrates that in vivo visualization of the interior of the right heart is feasible and that our angioscope can be used to assist placement of catheter at a specific location in the right atrium and to verify its location with no or minimal hemodynamic effects and without causing significant arrhythmias.
Angioscopes↗
Direct in vivo visualization of right cardiac anatomy by fibreoptic endoscopy: observation of radiofrequency-induced acute lesions around the ostium of the coronary sinus.
Current mapping techniques used during electrophysiological study involve catheter placement under fluoroscopic guidance and are associated with prolonged radiation exposure. We considered that direct visualization of right heart anatomy by means of fibreoptic endoscopy could be useful in accurately localizing and guiding the ablation of arrhythmogenic substrates. Our goal was to evaluate the ability of this device to safely and accurately visualize the ostium of the coronary sinus and its vicinity as well as radiofrequency-induced acute lesions. Anaesthetized dogs (n = 4) were studied. Multipolar electrode catheters and a 3.6 mm diameter fibreoptic endoscope with a latex balloon covering the distal tip were inserted into the right atrium. The blood pressure, and surface and intracardiac electrocardiograms were recorded simultaneously. Radiofrequency energy was delivered just inside the coronary sinus ostium or in its vicinity. The acute lesions were carefully observed by endoscopy. Postmortem examination was then performed. With a balloon volume of 7-10 ml, the visual field was 15-20 mm in diameter. The blood pressure was generally stable. The ostium of the coronary sinus and its vicinity were clearly and accurately identified, and catheter placement in the coronary sinus and its vicinity could be achieved under direct vision in all four dogs. Additionally, the process by which acute lesions were created by radiofrequency was also directly visualized in great detail. There was a good concordance between endoscopically observed images and postmortem findings, and there was a strong correlation between delivered energy and the volume of the radiofrequency-induced lesions (r = 0.895).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The v-Src SH3 domain binds phosphatidylinositol 3'-kinase.
Fibroblasts transformed by v-src or by related oncogenes encoding activated tyrosine kinases contain elevated levels of polyphosphoinositides with phosphate at the D-3 position of the inositol ring, as a result of the activation of phosphatidylinositol (PI) 3'-kinase. v-src-transformed cells also contain increased levels of PI 3'-kinase activity immunoprecipitable with anti-phosphotyrosine antibodies; furthermore, PI 3'-kinase can be detected in association with the v-Src tyrosine kinase. To identify regions of v-Src that can interact with PI 3'-kinase, the v-Src SH2 and SH3 domains were expressed in bacteria and incubated with lysates of normal chicken embryo fibroblasts. In vitro, the v-Src SH3 domain, but not the SH2 domain, bound PI 3'-kinase in lysates of uninfected chicken embryo fibroblasts. Substitutions of two highly conserved SH3 residues implicated in ligand binding abolished the ability of the v-Src SH3 domain to associate with PI 3'-kinase. Furthermore, the v-Src SH3 domain bound in vitro to the amino-terminal region of the p85 alpha subunit of PI 3'-kinase. These results suggest that the v-Src SH3 domain may mediate an interaction between the v-Src tyrosine kinase and PI 3'-kinase, by direct binding to p85.
Amino Acid Sequence↗
Multiple SH2-mediated interactions in v-src-transformed cells.
The Src homology 2 (SH2) domain is a noncatalytic region which is conserved among a number of signaling and transforming proteins, including cytoplasmic protein-tyrosine kinases and Ras GTPase-activating protein (GAP). Genetic and biochemical data indicate that the SH2 domain of the p60v-src (v-Src) protein-tyrosine kinase is required for full v-src transforming activity and may direct the association of v-Src with specific tyrosine-phosphorylated proteins. To test the ability of the v-Src SH2 domain to mediate protein-protein interactions, v-Src polypeptides were expressed as fusion proteins in Escherichia coli. The bacterial v-Src SH2 domain bound a series of tyrosine-phosphorylated proteins in a lysate of v-src-transformed Rat-2 cells, including prominent species of 130 and 62 kDa (p130 and p62). The p130 and p62 tyrosine-phosphorylated proteins that complexed v-Src SH2 in vitro also associated with v-Src in v-src-transformed Rat-2 cells; this in vivo binding was dependent on the v-Src SH2 domain. In addition to binding soluble p62 and p130, the SH2 domains of v-Src, GAP, and v-Crk directly recognized these phosphotyrosine-containing proteins which had been previously denatured and immobilized on a filter. In addition, the SH2 domains of GAP and v-Crk bound to the GAP-associated protein p190 immobilized on a nitrocellulose membrane. These results show that SH2 domains bind directly to tyrosine-phosphorylated proteins and that the Src SH2 domain can bind phosphorylated targets of the v-Src kinase domain.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.
Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-gamma, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.
Amino Acid Sequence↗
Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors.
Phospholipase C gamma 1 (PLC gamma 1) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLC gamma 1 and GAP contain two adjacent copies of the noncatalytic Src homology 2 (SH2) domain. The SH2 domains of PLC gamma 1 synthesized individually in bacteria formed high affinity complexes with the epidermal growth factor (EGF)- or platelet derived growth factor (PDGF)-receptors in cell lysates, and bound synergistically to activated receptors when expressed together as one bacterial protein. In vitro complex formation was dependent on prior growth factor stimulation and was competed by intracellular PLC gamma 1. Similar results were obtained for binding of GAP SH2 domains to the PDGF-receptor. The isolated SH2 domains of other signaling proteins, such as p60src and Crk, also bound activated PDGF-receptors in vitro. SH2 domains, therefore, provide a common mechanism by which enzymatically diverse regulatory proteins can physically associate with the same activated receptors and thereby couple growth factor stimulation to intracellular signal transduction pathways.
ErbB Receptors↗
Src homology region 2 domains direct protein-protein interactions in signal transduction.
Cytoplasmic proteins that regulate signal transduction or induce cellular transformation, including cytoplasmic protein-tyrosine kinases, p21ras GTPase-activating protein (GAP), phospholipase C gamma, and the v-crk oncoprotein, possess one or two copies of a conserved noncatalytic domain, Src homology region 2 (SH2). Here we provide direct evidence that SH2 domains can mediate the interactions of these diverse signaling proteins with a related set of phosphotyrosine ligands, including the epidermal growth factor (EGF) receptor. In src-transformed cells GAP forms heteromeric complexes, notably with a highly tyrosine phosphorylated 62-kDa protein (p62). The stable association between GAP and p62 can be specifically reconstituted in vitro by using a bacterial polypeptide containing only the N-terminal GAP SH2 domain. The efficient phosphorylation of p62 by the v-Src or v-Fps tyrosine kinases depends, in turn, on their SH2 domains and correlates with their transforming activity. In lysates of EGF-stimulated cells, the N-terminal GAP SH2 domain binds to both the EGF receptor and p62. Fusion proteins containing GAP or v-Crk SH2 domains complex with similar phosphotyrosine proteins from src-transformed or EGF-stimulated cells but with different efficiencies. SH2 sequences, therefore, form autonomous domains that direct signaling proteins, such as GAP, to bind specific phosphotyrosine-containing polypeptides. By promoting the formation of these complexes, SH2 domains are ideally suited to regulate the activation of intracellular signaling pathways by growth factors.
Animals↗
Growth and differentiation of the gubernaculum testis during testicular descent in the pig: changes in the extracellular matrix, DNA content, and hyaluronidase, beta-glucuronidase, and beta-N-acetylglucosaminidase activities.
The gubernaculum testis is a loose connective tissue organ that plays an essential mechanical role in testicular descent. In the pig, the first phase of descent (transabdominal migration) is brought about by growth of the gubernaculum through the inguinal canal into the scrotum and simultaneous somatic growth of the fetus. During the second phase the gubernaculum condenses, thus allowing the testis to descend into the scrotum. The nature of gubernaculum development (growth and differentiation) was investigated with respect to cell proliferation, extracellular matrix (ECM) composition, and acid hydrolases. Deoxyribonucleic acid (DNA) was used as a measure of cell number and hydroxyproline (HYP) was an estimate of interstitial collagen. The first phase of gubernaculum development was characterized by rapid cell proliferation and concomitant synthesis of sulphated glycosaminoglycans (S-GAG), hyaluronic acid (HA) and collagen. During the second phase cell proliferation ceased and DNA concentration increased. The amount of S-GAG remained closely related to the amount of DNA while HYP increased further. However, HA decreased during the second phase and thus HA metabolism seems to play a crucial role in biphasic development of the gubernaculum. The activities of the enzymes that are needed for biodegradation of HA (hyaluronidase, beta-glucuronidase and beta-N-acetylglucosaminidase) were measured in gubernaculum homogenate from animals during the first and second phase of testicular descent. These enzymes were detectable in gubernaculum and rose during the second phase of testicular descent. It was concluded that a very distinct dichotomy in the nature of gubernaculum development during the first and second phase could be discerned with respect to cell proliferation rate and ECM synthesis and degradation. These observations provide useful tools for future in vivo and in vitro investigations into the process and regulation of testicular descent.
Acetylglucosaminidase↗
The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function.
A conserved noncatalytic domain SH2 (for src homology region 2) is located immediately N terminal to the kinase domains of all cytoplasmic protein-tyrosine kinases. We found that the wild-type v-fps SH2 domain stimulated the enzymatic activity of the adjacent kinase domain 10-fold and functioned as a powerful positive effector of catalytic and transforming activities within the v-fps oncoprotein (P130gag-fps). Partial proteolysis of P130gag-fps and supporting genetic data indicated that the v-fps SH2 domain exerts its effect on catalytic activity through an intramolecular interaction with the kinase domain. Amino acid alterations in the SH2 domain that impaired kinase function interfered with association of the SH2 domain with the kinase domain. Deletion of a conserved octapeptide motif converted the v-fps SH2 domain from an activator to an inhibitor of tyrosine kinase activity. This latent inhibitory activity of v-fps SH2 has functional implications for phospholipase C-gamma and p21ras GTPase-activating protein, both of which have two distinct SH2 domains suggestive of complex regulation. In addition to regulating the specific activity of the kinase domain, the SH2 domain of P130gag-fps was also found to be required for the tyrosine phosphorylation of specific cellular proteins, notably polypeptides of 124 and 62 kilodaltons. The SH2 domain therefore appears to play a dual role in regulation of kinase activity and recognition of cellular substrates.
Amino Acid Sequence↗
Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity.
The catalytic domains of protein-tyrosine kinases such as the P130gag-fps oncoprotein contain the sequence HRDLAARN, followed thirteen residues C-terminal by DFG (P130gag-fps residues 1041-1048 and 1061-1063). These residues define a structural motif conserved among eucaryotic protein kinases (-RD----N, DFG) and shared with several procaryotic 3'aminoglycoside phosphotransferases (H-D----N, D-G). Functional analysis of mutant v-fps proteins employing bacterial and mammalian expression systems indicated that this motif is critical for P130gag-fps kinase activity and oncogenicity. In particular, conservative substitutions of the two invariant aspartates (asp1043, asp1061) with glutamate or asparagine completely eliminated enzymatic activity, suggesting that these residues are essential for catalysis. In contrast, substitution of arg1042 with glutamate decreased but did not eliminate v-fps kinase activity in bacteria. The effects of these and other amino acid substitutions within the phosphotransfer motif and at the nearby autophosphorylation site (tyr1073) of P130gag-fps indicate that these conserved residues are intrinsically essential to the execution or regulation of catalytic activity, and suggest that tight spatial constraints operate within the active centre of the v-fps tyrosine kinase domain.
Amino Acid Sequence↗