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Inositol-1,4,5-triphosphate receptors (IP(3)Rs) are ligand-gated Ca(2+) channels that control Ca(2+) release from intracellular stores. They are central to a wide range of cellular responses. IP(3)Rs in Caenorhabditis elegans are encoded by a single gene, itr-1, and are widely expressed. Signaling through IP(3) and IP(3)Rs is important in ovulation, control of the defecation cycle, modulation of pharyngeal pumping rate, and embryogenesis. To further elucidate the molecular basis of the diversity of IP(3)R function, we used a yeast two-hybrid screen to search for proteins that interact with ITR-1. We identified an interaction between ITR-1 and IRI-1, a previously uncharacterized protein with homology to LIN-15B. Iri-1 is widely expressed, and its expression overlaps significantly with that of itr-1. In agreement with this observation, iri-1 functions in known itr-1-mediated processes, namely, upregulation of pharyngeal pumping in response to food and control of the defecation cycle. Knockdown of iri-1 in an itr-1 loss-of-function mutant potentiates some of these effects and sheds light on the signaling pathways that control pharyngeal pumping rate. Knockdown of iri-1 expression also results in a sterile, evl phenotype, as a consequence of failures in early Z1/Z4 lineage divisions, such that gonadogenesis is severely disrupted.

Introduction: Other than discreet infra-clinical mucinous deposits observed during many inflammatory dermatoses, clinically visible dermal mucinosis can sometimes be associated with collagenosis. It is usually lupus and very rarely scleroderma. In this case, no confusion with papular mucinosis must be made., Case Report: A 51 year-old woman presented with infiltrated erythematous lesions in strips on the inner sides of the thighs and legs, associated with myalgia, arthralgia and puffy fingers. Mixed connective tissue disease was the initial diagnosis. The clinical picture was rapidly completed by sclerodactylia, telangiectasia, a Raynaud's syndrome and esophageal involvement leading to the diagnosis of CREST-type systemic scleroderma. The biopsy of the erythematous strip lesions revealed a dermal mucinosis. Treatment with hydroxychloroquine led to the regression of the mucinous lesions and the stabilization of the scleroderma, which, four years later, had not developed further., Discussion: Dermal mucinosis can accompany lupus erythematosus, in rare cases dermatomyositis and, in exceptional cases, scleroderma. The clinical presentation varies with large infiltrated plaques, reticulated or papulo-nodular lesions. Conversely, strip lesions such as those observed in our patient have never been reported till now. The association of a localized dermal mucinosis and a scleroderma must not lead to the erroneous diagnosis of papular mucinosis of clearly differing prognosis. The occurrence of a mucinosis during collagenosis might be related to enhanced synthesis of mucin by the fibroblasts mediated by the inflammatory cytokines, increased in this context.

Objectives: The Integrated Management of Childhood Illness (IMCI) approach and new clinical treatment guidelines to control malaria among children less than 5 years old were introduced recently in Cambodia. This study was conducted to finalize the malaria part of the national IMCI fever chart., Methods: A total of 323 sick children 2-59 months old were studied at rural health centres in northern Cambodia from February to April 2000. Cases with fever (by axillary temperature or history) or anaemia (by palmar pallor) were tested with dipsticks for Plasmodium falciparum and Plasmodium vivax in high and low malaria risk areas and, if positive, treated with anti-malarials., Results: The draft IMCI chart identified children with malaria safely and effectively (sensitivity 14 of 15, approximately 93% and specificity 292 of 308, approximately 95%). The study confirmed the potential of malaria dipsticks as a part of IMCI case management., Conclusion: The Cambodian Ministry of Health will use the studied malaria chart during the Early Implementation Phase of IMCI. Dipsticks able to detect P. falciparum and P. vivax with high sensitivity and acceptable cost will be needed for this purpose. To promote the rational use of dipsticks, the National Centre for Malaria Control, Parasitology and Entomology (Centre National de Malaridogie, Parasitologie et Entomologie, CNM) should list all known malaria risk areas in the country and prepare detailed local maps guiding case management especially in transitional zones.

Molecular and physiological studies of cells implicate interactions between the cytoskeleton and the intracellular calcium signalling machinery as an important mechanism for the regulation of calcium signalling. However, little is known about the functions of such mechanisms in animals. A key component of the calcium signalling network is the intracellular release of calcium in response to the production of the second messenger inositol 1,4,5-trisphosphate (IP(3)), mediated by the IP(3) receptor (IP(3)R). We show that C. elegans IP(3)Rs, encoded by the gene itr-1, interact directly with myosin II. The interactions between two myosin proteins, UNC-54 and MYO-1, and ITR-1 were identified in a yeast two-hybrid screen and subsequently confirmed in vivo and in vitro. We defined the interaction sites on both the IP(3)R and MYO-1. To test the effect of disrupting the interaction in vivo we overexpressed interacting fragments of both proteins in C. elegans. This decreased the animal's ability to upregulate pharyngeal pumping in response to food. This is a known IP(3)-mediated process [15]. Other IP(3)-mediated processes, e.g., defecation, were unaffected. Thus it appears that interactions between IP(3)Rs and myosin are required for maintaining the specificity of IP(3) signalling in C. elegans and probably more generally.

Inositol 1,4,5-trisphosphate (IP(3)) is an important second messenger in animal cells and is central to a wide range of cellular responses. The major intracellular activity of IP(3) is to regulate release of Ca(2+) from intracellular stores through IP(3) receptors (IP(3)Rs). We describe a system for the transient disruption of IP(3) signaling in the model organism Caenorhabditis elegans. The IP(3) binding domain of the C. elegans IP(3)R, ITR-1, was expressed from heat shock-induced promoters in live animals. This results in a dominant-negative effect caused by the overexpressed IP(3) binding domain acting as an IP(3) "sponge." Disruption of IP(3) signaling resulted in disrupted defecation, a phenotype predicted by previous genetic studies. This approach also identified two new IP(3)-mediated processes. First, the up-regulation of pharyngeal pumping in response to food is dependent on IP(3) signaling. RNA-mediated interference studies and analysis of itr-1 mutants show that this process is also IP(3)R dependent. Second, the tissue-specific expression of the dominant-negative construct enabled us to circumvent the sterility associated with loss of IP(3) signaling through the IP(3)R and thus determine that IP(3)-mediated signaling is required for multiple steps in embryogenesis, including cytokinesis and gastrulation.

To evaluate the risk of cancer among women with AIDS in New York City (NYC), we compared the cancer experience of AIDS-infected women in NYC with that of the general population of women in NYC by matching the population-based New York State Cancer Registry with the New York City AIDS Registry. A probabilistic algorithm was used to match names, birth dates, and, where available, Social Security numbers between 15,146 women with AIDS and 232,902 women with cancer. Standardized incidence ratios (SIR) were calculated as the ratio of observed to expected cancer cases in the population of NYC women matched for age, race, and calendar period of cancer diagnosis. Period-specific relative risks (RR) of cancer prevalence prior to AIDS, and incidence at or after AIDS were calculated to determine which cancers increased in proximity to an AIDS diagnosis, a surrogate marker of increasing immunodeficiency. Analysis was limited to women between the ages of 15 to 69 who were diagnosed with AIDS between 1981 and 1994. Among 15,146 women diagnosed with AIDS, we found 1,194 matches with the Cancer Registry. For cancers included in the 1993 AIDS case definition, the SIR was 178.49 for Kaposi's sarcoma, 48.97 for non-Hodgkin's lymphoma, and 9.20 for invasive cervical cancer. The overall SIR for all non-AIDS-defining cancers was 2.20. Among non-AIDS-defining cancers, elevated SIRs were found for cancers of the lung (7.95), esophagus (7.69), multiple myeloma (7.37), oral cavity and pharynx (6.55), Hodgkin's disease (5.65), leukemias (4.52), and rectal/anal cancers (3.23). Statistically significant increases in period-specific risks were found for all non-AIDS-defining cancers combined, but not for individual cancers. Dual screening by two registries and unknown behavioral factors complicate the ascertainment of cancer risk. Our results show significantly elevated risks for several non-AIDS-defining cancers; these results are consistent with other studies of cancers among persons with AIDS. Extension of the time period of analysis is required to test for the effects of new anti-viral treatments and their association with cancer development among HIV-infected women.

The "Lab-on-a-Cable" concept, based on scaling down an electrochemical flow system to a cable platform, is described. The system integrates the analyte collection and the sample handling, with the electrochemical detection of the reaction product in a sealed cylindrical unit, connected to a long shielded cable. An enzymatic assay, involving collection of a phenolic substrate, its mixing with an internally delivered tyrosinase solution, and amperometric detection of the liberated quinone product, is used for illustrating the operation of the flow probe and demonstrating its advantages over remote phenol sensors. The internal buffer solution ensures independence of sample conditions such as pH, ionic strength, or natural conditions, that commonly influences the performance of remote sensors. The "built-in" flow pulsation of the integrated micropump is exploited for a sensitive hydrodynamic-modulation voltammetric detection of hydrazine and peroxide pollutants.

A 42-year-old woman, who had undergone excision of a melanoma of her right forearm 3 years before (Breslow's index 4.4 mm), was admitted to hospital for the evaluation of an superior vena cava syndrome. The thoracic CT scan and the phlebography showed obstruction of the superior vena cava by an endovascular tumor. Abdominal, pelvis and cranial CT scans did not reveal any other metastatic localization. Surgery with extracorporeal circulation was performed. The mass was resected and histopathologic examination confirmed the endovascular metastatic melanoma. There was no heart metastasis. The patient was then given a polychemotherapy. She was still alive after 18 months of follow-up after the initial metastasis. To our knowledge, no similar case has previously been reported and surgical treatment, as for isolated heart metastatic melanoma, may be considered for vascular metastasis, as in our case.

Recently Sports Medicine Australia (SMA) and the Australian Association for Exercise and Sport Science (AAESS) developed guidelines for pre-exercise screening and supervision of fitness testing, based on the American College of Sports Medicine (ACSM) system. The procedure involves classifying individuals into one of three risk groups (apparently healthy, at higher risk, with known disease). Using data collected in a 1992 survey of 2298 Australian adults aged 18-78 years conducted by the Department of the Arts, Sport, the Environment and Territories (DASET), we calculated the percentage of the general population falling within each risk group and therefore exclusion rates (ie the proportion of subjects who, it is recommended, would require medical clearance prior to exercise or exercise testing). The analysis of data found that between 43-73% of males and 44-61% of females would require clearance. A cost analysis suggests that a rigorous application of the SMA-AAESS guidelines would cost between $250 million and $1.2 billion each year. On the basis of the results, suggestions for reviewing the guidelines have been proposed.

A general method for obtaining high-level production of low molecular weight proteins in Escherichia coli is described. This method is based on the use of a novel Met-Xaa-protein construction which is formed by insertion of a single amino acid residue (preferably Arginine or Lysine) between the N-terminal methionine and the protein of interest. The utility of this method is illustrated by examples for achieving high-level production of human insulin-like growth factor-1, human proinsulin, and their analogs. Furthermore, highly produced insulin-like growth factor-1 derivatives and human proinsulin analogs are converted to their natural sequences by removal of dipeptides with cathepsin C.

The association of Sweet's syndrome and Crohn's disease is rare. We report a new case of such association. A 45 year-old woman developed a diarrhea, fever, and skin lesions consistent with a presumptive diagnosis of Sweet's syndrome. Crohn's disease was also diagnosed. Oral prednisone, associated with mesalazine, effected improvement of both cutaneous lesions and bowel disease. The ten cases of the literature and ours show that Sweet's syndrome may occur during an acute phase of Crohn's disease. Most of the time, Crohn's disease has already been diagnosed. However, this was not so with our patient, wherein lies the originality of our case. A general corticotherapy is the preferred course of treatment.

Introduction: Among the cutaneous manifestations of the Churg-Strauss syndrome, palpable purpura of the extremities is the most common. Although they are not specific, sub-cutaneous nodules of the scalp are the most distinctive lesions., Case Report: A 58 year-old man, with a 7-years history of asthma, developed profuse cutaneous lesions involving the face and the scalp, initially erythematosus and vesiculous, then purpuric and necrotic which led to the diagnostic of Churg-Strauss syndrome., Commentary: Cutaneous lesions occur frequently during the Churg-Strauss syndrome and may reveal the disease as in our patient. However, the initial clinical presentation was uncommon with erythematosus and vesiculous lesions mimicking primary herpes infection. Cutaneous biopsy was useful leading to an early diagnosis.

1. Binding of the specific bradykinin B1 receptor agonist, [3H]-des-Arg10-kallidin (-KD) was investigated in smooth muscle cells (SMC) isolated from rabbit mesenteric arteries (RMA). 2. [3H]-des-Arg10-KD specifically bound to interleukin-1 (IL-1)-treated RMA-SMC in a saturable fashion with an equilibrium dissociation constant (KD) of 0.3-0.5 nM. The number of binding sites per cell was 20,000-35,000. Kinins inhibited [3H]-des-Arg10-KD binding to RMA-SMC with an order of potency very similar to that observed in typical B1 specific bioassays: des-Arg9-bradykinin (BK) approximately KD >> BK. Furthermore, the B1 receptor antagonist [Leu8]des-Arg9-BK inhibited [3H]-des-Arg10-KD binding with an IC50 of 43 nM as expected for its effect at B1 receptors. The B2 receptor antagonists, NPC 567 and Hoe 140 only affected [3H]-des-Arg10-KD binding at very high concentrations (IC50 = 0.8 microM and IC50 > 10 microM, respectively). 3. Des-Arg9-BK (B1 agonist) and [Hyp3]Tyr(Me)8-BK (B2 agonist) did not induce prostacyclin (PGI2) production by RMA-SMC. Lipopolysaccharide (LPS) treatment of the cells did not affect the B1 agonist response whereas IL-1 beta treatment produced a 7 fold increase in des-Arg9-BK-stimulated PGI2 production. IL-1 beta also stimulated the response to B2 agonists. 4. Des-Arg9-BK-induced PGI2 secretion in IL-1-primed RMA-SMC was mediated by B1 receptors since it was inhibited by [Leu8]des-Arg9-BK (IC50 = 56-73 nM) but not by Hoe 140. High concentrations of NPC 567 (IC5o = 2.4 micro M) were required to inhibit PGI2 production induced by B1 agonists.5. IL- 1-treated RMA-SMC displayed a 5 fold increase in the number of B1 receptors without modification of the affinity constant, thus establishing a possible relationship between the receptor density and the IL-i-primed B1 response.6. LPS treatment of the cells induced a 4 fold increase in B1 receptor number without modifying PGI2 secretion. This observation suggests that IL-1 but not LPS, in addition to increase in the number of receptors, signals the cell to permit the coupling of B1 receptors to the PLA2/cyclo-oxygenase pathway.

1,25-dihydroxyvitamin D3[1,25(OH)2D3] effects on bone resorption in organ culture and on 45Ca2+ efflux rates in bone cells were measured in presence of a calcium channel inhibitor, diltiazem. Though, diltiazem reduced the 45Ca release from mice calvaria it did not act at the same Ca compartment as 1,25(OH)2D3 to alter Ca2+ flux parameters. It therefore seems difficult to hypothesize a simple relationship between bone resorption and Ca2+ movements in bone cells.

We have undertaken a microanatomical study of a new donor site--the posterior forearm territory--on 43 cadaver arms. Two axial arteries were found, and both the fasciocutaneous flap and the fascial flap could be elevated with the two arteries on the posterior forearm. The posterior forearm flap was transferred to the hand to repair deformities of the wrist, the first web space, the dorsal hand, and the metacarpophalangeal joints in eight cases. The result was very satisfactory. The posterior forearm flap is near the hand, easy to perform, and reliable. It is a one-stage operation and does not sacrifice a main artery. In this article we demonstrate our own ideas about flap extension, which is valuable for clinical application.