D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor.

We provided evidence for the formation of a novel phospholipase C-mediated calcium signal arising from coactivation of D1 and D2 dopamine receptors. In the present study, robust fluorescence resonance energy transfer showed that these receptors exist in close proximity indicative of D1-D2 receptor heterooligomerization. The close proximity of these receptors within the heterooligomer allowed for cross-phosphorylation of the D2 receptor by selective activation of the D1 receptor.

Predictors of multi-organ dysfunction in heatstroke.

Background: Heatstroke is a medical emergency that results from failure of thermoregulatory mechanism coupled with an exaggerated acute phase response, causing an elevation in core body temperature that rises above 40 degrees C, producing multi-organ dysfunction. It carries a high mortality rate, and in survivors, a risk of permanent neurological damage.

Objective: To investigate predictors of multiple organ dysfunction syndrome in patients presenting with heatstroke.

Cloning and characterisation of an aspartyl protease inhibitor (API-1) from Ancylostoma hookworms.

Hookworm infection persists as a public health problem in developing nations. Vaccine-based strategies offer the best chance of long-term control. Aspartyl protease inhibitors from parasitic nematodes are highly immunogenic, and have been suggested as potential vaccine antigens.

Dynamics of anti-M antibody response in a mouse model following intranasal infection with group A Streptococcus M-18.

Dynamics of anti-M antibody response following intranasal infection with group A Streptococcus (GAS) M-18 were investigated in a Swiss albino mouse model. Mice arranged in three groups were inoculated intranasally with 2.0x10(7) c.

Intermediate colloidal formation and the varying width of periodic precipitation bands in reaction-diffusion systems.

The mechanism of rhythmic pattern formation in reaction-diffusion systems is investigated theoretically by introducing a new concept. The boundary that separates the two reacting species virtually migrates as the diffusion proceeds into the gelatinous medium. Based on this boundary migration scenario, all the well-established relations on Liesegang patterns could be proved, in a rather modified way.

How does a femoral varus osteotomy alter the natural evolution of Perthes' disease?

To study how a femoral osteotomy alters the natural evolution of Perthes' disease, records and radiographs of 640 patients with Perthes' disease were analyzed. The data of 314 patients who underwent femoral osteotomy were compared with those of non-operated patients. A new modification of classification of the stages of evolution of the disease was used to identify the timing of surgery and to monitor the progress of the disease following surgery.

Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal.

Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine receptors, several lines of evidence indicate that they are functionally linked. However, a mechanism for this linkage has not been elucidated. In this study, we demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone or when only one of the co-expressed receptors was activated by a selective agonist.

Pacemaker endocarditis caused by Pseudomonas aeruginosa treated successfully.

Infective endocarditis (IE) is a rare but serious complication of permanent cardiac pacemaker placement. Endocarditis in the presence of prosthetic valves and pacemakers is usually due to staphylococci. We present a case of pacemaker endocarditis caused by Pseudomonas aeruginosa that was successfully treated with a combination of antimicrobial therapy and percutaneous removal of the colonized lead.

Blockade of G protein-coupled receptors and the dopamine transporter by a transmembrane domain peptide: novel strategy for functional inhibition of membrane proteins in vivo.

G protein-coupled receptors have a core consisting of seven transmembrane alpha-helices that is important in maintaining the structure of the receptor. We postulated that disruption of the transmembrane core may interfere with receptor function. In this study, the function of integral membrane proteins was disrupted in vivo using peptides mimicking their transmembrane domains.

Optimal timing for containment surgery for Perthes disease.

To identify the optimal timing for containment surgery for Perthes disease, the outcomes following femoral osteotomy of 97 children were analyzed. Univariate and multivariate analyses were employed to identify variables that influenced the shape and size of the femoral head at healing. The timing of surgery was an important variable that had a bearing on the outcome.

Natural evolution of Perthes disease: a study of 610 children under 12 years of age at disease onset.

Records and 2,634 pairs of radiographs (anteroposterior and lateral) of 610 patients with Perthes disease were reviewed. The evolution of the disease was divided into seven stages (stages Ia, Ib, IIa, IIb, IIIa, IIIb, and IV) based on plain radiographic appearances. Intraobserver and interobserver reproducibility of this new classification system was assessed.

Post-exposure prophylaxis for blood borne viral infections in healthcare workers.

Healthcare workers have a high risk of occupational exposure, more so in developing countries, with high incidence of blood borne diseases and prevalence of unsafe practices. Among the various blood borne diseases, the most common and important ones are HIV infection, hepatitis B, and hepatitis C. Most of the occupational transmission can be prevented and the "standard precaution" has been shown to reduce exposures and hence the transmission of infection.

Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome.

Sudden unexplained nocturnal death syndrome (SUNDS), a disorder found in southeast Asia, is characterized by an abnormal electrocardiogram with ST-segment elevation in leads V1-V3 and sudden death due to ventricular fibrillation, identical to that seen in Brugada syndrome. We screened patients with SUNDS for mutations in SCN5A, the gene known to cause Brugada syndrome, as well as genes encoding ion channels associated with the long-QT syndrome. Ten families were enrolled, and screened for mutations using single-strand DNA conformation polymorphism analysis, denaturing high-performance liquid chromatography and DNA sequencing.

Distinct residues in the carboxyl tail mediate agonist-induced desensitization and internalization of the human dopamine D1 receptor.

We have shown in a previous study that desensitization and internalization of the human dopamine D(1) receptor following short-term agonist exposure are mediated by temporally and biochemically distinct mechanisms. In the present study, we have used site-directed mutagenesis to remove potential phosphorylation sites in the third intracellular loop and carboxyl tail of the dopamine D(1) receptor to study these processes. Mutant D(1) receptors were stably transfected into Chinese hamster ovary cells, and kinetic parameters were measured.

Perthes' disease in the adolescent.

We studied the natural history of Perthes' disease in 62 children in whom the onset of symptoms was in adolescence. Three patterns of disease were noted, namely, late-onset pattern, segmental collapse, or destructive with failure of revascularisation. In the late-onset pattern, the disease followed the sequence of healing seen in younger children, but adequate epiphyseal remodelling did not occur.

Nerve and muscle disorders and their sequelae.

A number of diseases of the nervous system, especially upper neuron lesions, produce ankle and foot deformities. Such deformities can be the single most important reason why some patients become nonambulatory. This article reviews the impact of upper motor neuron lesions such as traumatic brain injury, stroke, multiple sclerosis, neurodegenerative disorders, and low motor neuron lesions such as peripheral nerve injury, neuropathy, entrapment syndromes, and muscle diseases.

Clausa, a tomato mutant with a wide range of phenotypic perturbations, displays a cell type-dependent expression of the homeobox gene LeT6/TKn2.

Class I knox genes play an important role in shoot meristem function and are thus involved in the ordered development of stems, leaves, and reproductive organs. To elucidate the mechanism underlying the expression pattern of these homeobox genes, we studied a spontaneous tomato (Lycopersicon esculentum) mutant that phenotypically resembles, though is more extreme than, transgenic plants misexpressing class I knox genes. This mutant was found to carry a recessive allele, denoted clausa:shootyleaf (clau:shl)-a newly identified allele of clausa.

Oligomerization of dopamine and serotonin receptors.

Until recently, it has largely been assumed that G protein-coupled receptors (GPCRs) function as monomeric entities. However, over the past few years, we and others have documented that GPCRs can form dimers and oligomers, leading to a re-evaluation of the mechanisms thought to mediate GPCR function. Despite the growing number of investigations into dimerization, little is known about the structural basis of receptor-receptor interactions and the functional consequences of dimer formation.

Inhibition of cell surface expression by mutant receptors demonstrates that D2 dopamine receptors exist as oligomers in the cell.

Numerous mutant G protein-coupled receptors with diminished or no function have been described that are naturally occurring or that are the product of gene manipulation. It has largely been assumed that receptor mutants do not affect the function of the wild-type receptor; however, the occurrence of G protein-coupled receptor dimerization suggests the possibility that an intermolecular interaction between mutant and wild-type receptors can occur. We have shown previously that the D2 dopamine receptor (D2DR) exists as dimers in cell lines and brain tissue.

Oligomerization of mu- and delta-opioid receptors. Generation of novel functional properties.

The existence of dimers and oligomers for many G protein-coupled receptors has been described by us and others. Since many G protein-coupled receptor subtypes are highly homologous to each other, we examined whether closely related receptors may interact with each other directly and thus have the potential to create novel signaling units. Using mu- and delta-opioid receptors, we show that each receptor expressed individually was pharmacologically distinct and could be visualized following electrophoresis as monomers, homodimers, homotetramers, and higher molecular mass oligomers.

Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.

Medical education: Nasal endoscope and you.

Although much has been written about the surgical technique of functional endoscopic sinus surgery, for sinusitis and nasal polyposes, the other uses of the nasal endoscope has not been mentioned, Seven hundred and twenty five patients have undergone endoscopic nasal office evaluations and subsequent functional endoscopic sinus surgery for various indications in our unit from December 1990 to September 1994. Though most of the surgeries were for nasal polyposes and sinusitis, we have used the scope for various other indications.