Pyoderma gangrenosum associated with myelofibrosis.
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Aged↗
Biomedical subjects
R Finkelstein
Publications and source records attributed to R Finkelstein.
Mechanism of cross-contamination of blood culture bottles in a pseudoepidemic of Enterobacter cloacae bacteremia.
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Bacteremia↗
Targeting gene expression to the head: the Drosophila orthodenticle gene is a direct target of the Bicoid morphogen.
The Bicoid (Bcd) morphogen establishes the head and thorax of the Drosophila embryo. Bcd activates the transcription of identified target genes in the thoracic segments, but its mechanism of action in the head remains poorly understood. It has been proposed that Bcd directly activates the cephalic gap genes, which are the first zygotic genes to be expressed in the head primordium. It has also been suggested that the affinity of Bcd-binding sites in the promoters of Bcd target genes determines the posterior extent of their expression (the Gene X model). However, both these hypotheses remain untested. Here, we show that a small regulatory region upstream of the cephalic gap gene orthodenticle (otd) is sufficient to recapitulate early otd expression in the head primordium. This region contains two control elements, each capable of driving otd-like expression. The first element has consensus Bcd target sites that bind Bcd in vitro and are necessary for head-specific expression. As predicted by the Gene X model, this element has a relatively low affinity for Bcd. Surprisingly, the second regulatory element has no Bcd sites. Instead, it contains a repeated sequence motif similar to a regulatory element found in the promoters of otd-related genes in vertebrates. Our study is the first demonstration that a cephalic gap gene is directly regulated by Bcd. However, it also shows that zygotic gene expression can be targeted to the head primordium without direct Bcd regulation.
Animals↗
Murine Otx1 and Drosophila otd genes share conserved genetic functions required in invertebrate and vertebrate brain development.
Despite the obvious differences in anatomy between invertebrate and vertebrate brains, several genes involved in the development of both brain types belong to the same family and share similarities in expression patterns. Drosophila orthodenticle (otd) and murine Otx genes exemplify this, both in terms of expression patterns and mutant phenotypes. In contrast, sequence comparison of OTD and OTX gene products indicates that homology is restricted to the homeodomain suggesting that protein divergence outside the homeodomain might account for functional differences acquired during brain evolution. In order to gain insight into this possibility, we replaced the murine Otx1 gene with a Drosophila otd cDNA. Strikingly, epilepsy and corticogenesis defects due to the absence of Otx1 were fully rescued in homozygous otd mice. A partial rescue was also observed for the impairments of mesencephalon, eye and lachrymal gland. In contrast, defects of the inner ear were not improved suggesting a vertebrate Otx1-specific function involved in morphogenesis of this structure. Furthermore, otd, like Otx1, was able to cooperate genetically with Otx2 in brain patterning, although with reduced efficiency. These data favour an extended functional conservation between Drosophila otd and murine Otx1 genes and support the idea that conserved genetic functions required in mammalian brain development evolved in a primitive ancestor of both flies and mice.
Animals↗
Equivalence of the fly orthodenticle gene and the human OTX genes in embryonic brain development of Drosophila.
Members of the orthodenticle gene family are essential for embryonic brain development in animals as diverse as insects and mammals. In Drosophila, mutational inactivation of the orthodenticle gene results in deletions in anterior parts of the embryonic brain and in defects in the ventral nerve cord. In the mouse, targeted elimination of the homologous Otx2 or Otx1 genes causes defects in forebrain and/or midbrain development. To determine the morphogenetic properties and the extent of evolutionary conservation of the orthodenticle gene family in embryonic brain development, genetic rescue experiments were carried out in Drosophila. Ubiquitous overexpression of the orthodenticle gene rescues both the brain defects and the ventral nerve cord defects in orthodenticle mutant embryos; morphology and nervous system-specific gene expression are restored. Two different time windows exist for the rescue of the brain versus the ventral nerve cord. Ubiquitous overexpression of the human OTX1 or OTX2 genes also rescues the brain and ventral nerve cord phenotypes in orthodenticle mutant embryos; in the brain, the efficiency of morphological rescue is lower than that obtained with overexpression of orthodenticle. Overexpression of either orthodenticle or the human OTX gene homologs in the wild-type embryo results in ectopic neural structures. The rescue of highly complex brain structures in Drosophila by either fly or human orthodenticle gene homologs indicates that these genes are interchangeable between vertebrates and invertebrates and provides further evidence for an evolutionarily conserved role of the orthodenticle gene family in brain development.
Animals↗
Be a leader, not a victim in changing access world. Need for separate department may end.
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Admitting Department, Hospital↗
Novel segment polarity gene interactions during embryonic head development in Drosophila.
In the trunk of the Drosophila embryo, the segment polarity genes are initially activated by the pair-rule genes, and later maintain each other's expression through a complex network of cross-regulatory interactions. These interactions, which are critical to cell fate specification, are similar in each of the trunk segments. To determine whether segment polarity gene expression is established differently outside the trunk, we studied the regulation of the genes hedgehog (hh), wingless (wg), and engrailed (en) in each of the segments of the developing head. We show that the cross-regulatory relationships among these genes, as well as their initial mode of activation, in the anterior head are significantly different from those in the trunk. In addition, each head segment exhibits a unique network of segment polarity gene interactions. We propose that these segment-specific interactions evolved to specify the high degree of structural diversity required for head morphogenesis.
Animals↗
[Acute fungal endocarditis due to Trichosporon beigelli].
We report a 59-year-old woman with acute fungal endocarditis of a prosthetic valve caused by the endogenic organism, Trichosporon beigelli. This slowly developing disease mainly effects drug addicts who use intravenous narcotics. In nonaddicts it is rare, with mortality as high as 50%. There are only sporadic reports of T. beigelli as a complication long after open heart surgery. The ongoing infection is undetected for even years after the primary infection, due to its prolonged latent phase. We present the difficulties of diagnosis, and of treating the disease with a combination of surgery and of long-term chemotherapy.
Acute Disease↗
Pulmonary infiltrates and skin lesions.
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Bone Neoplasms↗
Detection of expiratory flow limitation during exercise in COPD patients.
The negative expiratory pressure (NEP) method was used to detect expiratory flow limitation at rest and at different exercise levels in 4 normal subjects and 14 patients with chronic obstructive pulmonary disease (COPD). This method does not require performance of forced expirations, nor does it require use of body plethysmography. It consists in applying negative pressure (-5 cmH2O) at the mouth during early expiration and comparing the flow-volume curve of the ensuing expiration with that of the preceding control breath. Subjects in whom application of NEP does not elicit an increase in flow during part or all of the tidal expiration are considered flow limited. The four normal subjects were not flow limited up to 90% of maximal exercise power output (Wmax). Five COPD patients were flow limited at rest, 9 were flow limited at one-third Wmax, and 12 were flow limited at two-thirds Wmax. Whereas in all patients who were flow limited at rest the maximal O2 uptake was below the normal limits, this was not the case in most of the other patients. In conclusion, NEP provides a rapid and reliable method to detect expiratory flow limitation at rest and during exercise.
Adult↗
Severe minocycline-induced eosinophilic pneumonia: extrapulmonary manifestations and the use of in vitro immunoassays.
OBJECTIVE: To report a severe and unusual reaction to minocycline and the use of in vitro immunologic assays. CASE SUMMARY: A 46-year-old white man developed severe respiratory distress with pulmonary infiltrates on chest X-ray and eosinophilia in blood, bronchoalveolar lavage fluid, and biopsied lung tissue during exposure to minocycline. Additional manifestations included pleuropericardial effusion, liver function abnormality, and bone marrow eosinophilia. Macrophage inhibition factor and mast cell degranulation assays were positive to minocycline. DISCUSSION: The patient's manifestations were compatible with the diagnosis of eosinophilic pneumonia. After excluding other possible etiologies, minocycline was identified as the offending agent. Generalized damage was suggested by the presence of a combination of extrapulmonary manifestations previously not reported. Results of the in vitro immunologic assays supported the hypersensitivity nature of the disease and confirmed the diagnosis. CONCLUSIONS: Minocycline-induced eosinophilic pneumonia may involve extrapulmonary sites. It is suggested that in vitro immunoassays be used for confirmation of the diagnosis rather than rechallenge or invasive procedures.
Anti-Bacterial Agents↗
Establishing primordia in the Drosophila eye-antennal imaginal disc: the roles of decapentaplegic, wingless and hedgehog.
The eye-antennal imaginal discs of Drosophila melanogaster form the head capsule of the adult fly. Unlike the limb primordia, each eye-antennal disc gives rise to morphologically and functionally distinct structures. As a result, these discs provide an excellent model system for determining how the fates of primordia are specified during development. In this study, we investigated how the adjacent primordia of the compound eye and dorsal head vertex are specified. We show that the genes wingless (wg) and orthodenticle (otd) are expressed throughout the entire second instar eye-antennal disc, conferring a default fate of dorsal vertex cuticle. Activation of decapentaplegic (dpp) expression in the posterior eye disc eliminates wg and otd expression, thereby permitting eye differentiation. We also demonstrate that otd is activated by wg in the vertex primordium. Finally, we show that early activation of dpp depends on hedgehog (hh) expression in the eye anlage prior to morphogenetic furrow formation.
Animals↗
[Drug fever].
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Body Temperature Regulation↗
Orthodenticle regulation during embryonic head development in Drosophila.
The homeobox gene orthodenticle (otd) specifies anterior head development in the Drosophila embryo, otd-related genes are also found in vertebrates, with expression patterns suggesting that they are important for the development of anterior regions of the head and brain. Here, we analyze the molecular mechanisms by which otd expression is activated within its normal domain in the head and repressed outside this region. We demonstrate that, contrary to early models of embryonic pattern formation, high levels of the bicoid morphogen are not required for otd activation or for the establishment of anterior head structures. We also show that the terminal system contributes to otd activation in the head primordium. Finally, we identify a novel pathway mediated by the gap gene huckebein through which three maternal systems cooperate to repress otd expression at the anterior terminus of the embryo.
Animals↗
Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.
We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.
Adult↗
Brain abscesses: the lung connection.
Pulmonary arteriovenous fistulas are uncommon abnormalities of capillary development which cause right to left shunting and, if not treated, may lead to severe neurological complications, including meningitis and brain abscess. Pulmonary arteriovenous fistulas are commonly a result of hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease) and both conditions may be readily diagnosed by careful history taking and physical examination. Two cases of brain abscess associated with hereditary haemorrhagic telangiectasia, which remained unrecognized for many years, are reported. These cases emphasize the importance of early diagnosis and treatment of pulmonary arteriovenous fistula in preventing central nervous system infections.
Adult↗
Failure of cefonicid prophylaxis for infectious complications related to endoscopic retrograde cholangiopancreatography.
We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis.
Bacteremia↗
hedgehog, wingless and orthodenticle specify adult head development in Drosophila.
The adult head capsule of Drosophila forms primarily from the eye-antennal imaginal discs. Here, we demonstrate that the head primordium is patterned differently from the discs which give rise to the appendages. We show that the segment polarity genes hedgehog and wingless specify the identities of specific regions of the head capsule. During eye-antennal disc development, hedgehog and wingless expression initially overlap, but subsequently segregate. This regional segregation is critical to head specification and is regulated by the orthodenticle homeobox gene. We also show that orthodenticle is a candidate hedgehog target gene during early eye-antennal disc development.
Animals↗