Pulseless foot after stab wound to the calf: clue to a therapeutically important arterial variant.
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Biomedical subjects
Publications and source records attributed to N H Patel.
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We have cloned and characterized the Antennapedia (Antp) gene from the grasshopper Schistocerca americana. The Antennapedia protein contains seven blocks of sequence, including the homeodomain, that are conserved in the homologous proteins of other insects, interspersed with (usually repetitive) sequences unique to each species. There is no similarity between 1.8 kb of 3' untranslated sequence in grasshopper and Drosophila. We examined Antennapedia protein expression in grasshopper using an antibody raised against a grasshopper fusion protein and reexamined its expression in Drosophila using several different antibodies. Early patterns of expression in the two insects are quite different, reflecting differing modes of early development. However, by the germband stage, expression patterns are quite similar, with relatively uniform epithelial expression throughout the thoracic and abdominal segments which later retracts to the thorax. Expression is observed in muscle pioneers, the peripheral nervous system, and the central nervous system (CNS). In the CNS expression is initially limited to a few neurons, but eventually becomes widespread. Both insects show strong expression in certain homologous identified neurons and similar temporal modulation of expression.
RATIONALE AND OBJECTIVES: The radiology report is the primary means of communication between the radiologist and the referring physician. A lack of precision in this report may adversely affect patient care. We examined how radiologists would define "nonspecific abdominal gas pattern" and how referring physicians would perceive the meaning. METHODS: A questionnaire was distributed to radiologists and referring physicians in Flint, Michigan. They were asked to categorize their definition or interpretation, respectively, of "nonspecific abdominal gas pattern" into "normal"; "either normal or abnormal"; or "abnormal, representing either mechanical obstruction or adynamic ileus." RESULTS: Thirty-three radiologists responded, 23 (69.7%) of whom used the term. One hundred fifty-seven referring physicians responded, 127 of whom assigned a specific definition to the term. Using a 2 x 3 chi-square test (df = 2), we found a statistically significant difference (p < .03) between the distribution of the meaning of the term between radiologists and their referring physicians. CONCLUSION: The term "nonspecific abdominal gas pattern" should be abandoned because it may signify a normal condition or a pathologic state. We found the definition to be dichotomous and asynchronous between radiologists and their referring physicians.
A patient with complaints of right foot pain and previous normal radiographs had an abnormal three-phase bone scan consistent with a second metatarsal stress fracture. Subsequent radiographs confirmed this diagnosis. Two months later, the patient developed pain in his left foot, and again initial radiographs were noncontributory. A later bone scan revealed a left second metatarsal stress fracture. The results in this case reemphasize the value of bone scintigraphy in patients with foot pain and no bone abnormalities on plain radiographs.
Rapid advances have been made in the understanding of the genetic basis of development and pattern formation in a variety of model systems. By examining the extent to which these developmental systems are conserved or altered between different organisms, insight can be gained into the evolutionary events that have generated the diversity of organisms around us. The molecular and genetic basis of early pattern formation in Drosophila melanogaster has been particularly well studied, and comparisons to other insects have revealed conservation of some aspects of development, as well as differences that may explain variations in early patterning events.
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We report the identification of a Drosophila locus, reversed polarity (repo). Weak repo alleles were viable but affected glia in the optic lobe, resulting in a reversal in polarity of the electrophysiological to light in the adult. Strong repo alleles caused defects in embryonic glia and resulted in embryonic lethality. Expression of repo appeared to be specific to glia throughout development. In the adult visual system, repo was expressed in laminal glia, medullar glia, and subretinal cells; in the embryo, repo was expressed in nearly all of the identified glia in the central and peripheral nervous systems except midline glia. The repo gene encoded a homeo domain protein suggesting that it might be a transcriptional regulator of genes required for glial development.
Now that the genes controlling embryonic patterning have been identified in several model organisms, long-standing questions concerning the evolution of developmental systems are open to investigation. Examination of the expression of even-skipped in a variety of insects reveals that Insect germ-type designations apparently do not reflect the variations in the mechanisms of segmentation evident throughout insect phylogeny.
We have cloned and sequenced the single Tribolium homolog of the Drosophila engrailed gene. The predicted protein contains a homeobox and several domains conserved among all engrailed genes identified to date. In addition it contains several features specific to the invected homologs of Bombyx and Drosophila, indicating that these features most likely were present in the ancestral gene in the common ancestor of holometobolous insects. We used the cross-reacting monoclonal antibody, 4D9, to follow the expression of the Engrailed protein during segmentation in Tribolium embryos. As in other insects, Engrailed accumulates in the nuclei of cells along the posterior margin of each segment. The first Engrailed stripe appears as the embryonic rudiment condenses. Then as the rudiment elongates into a germ band, Engrailed stripes appear in an anterior to posterior progression, just prior to morphological evidence of the formation of each segment. As in Drosophila (a long germ insect), expression of engrailed in Tribolium (classified as a short germ insect) is preceded by the expression of several homologous segmentation genes, suggesting that similar genetic regulatory mechanisms are shared by diverse developmental types.
Resistance to chemotherapy is the single most important reason for treatment failure in cancer patients. Over the past 15 years, we have gained significant insight into one of the mechanisms responsible for this process: multidrug resistance (MDR). Far from being a phenomenon limited to the laboratory, multidrug resistance has been identified in a wide variety of newly diagnosed and recurrent human tumors. A number of compounds can block p-glycoprotein and overcome MDR in vitro and in vivo. Current strategies to block MDR are discussed in this review. Future research in this area will focus on the identification of more selective and potent MDR reversing agents and the development of entirely new approaches to overcoming multidrug resistance such as monoclonal antibodies, immunotoxins, and gene therapy.
The molecular mechanisms involved in glial/neuronal fate decisions during embryonic development are largely unknown. Here we show that the segment-polarity gene engrailed, which encodes a homeodomain protein, controls these decisions within an insect CNS lineage. The grasshopper median neuroblast (MNB) generates both neurons and midline glia in distinct temporal phases. engrailed expression in MNB progeny can be inhibited by injection of antisense oligodeoxynucleotides into the MNB nucleus. This produces a phenotype in which the midline glia do not develop and extra midline neurons are generated. In the absence of engrailed function, midline glial precursors are apparently converted into neuronal precursors. Thus, engrailed is required for execution of the decision between the glial and neuronal fates.
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We have identified a novel homeodomain gene, buttonless (btn), that is specifically expressed in 20 cells of a single type during Drosophila embryonic development. These cells, the dorsal median (DM) cells, are arranged as a single pair within each segment along the dorsal midline of the CNS. Distinctive features of the DM cells include a large cell body and a long thick process extending laterally to the muscle attachment site. In the absence of btn gene function the initial commitment to the DM cell fate is made but differentiation fails to occur and the DM cells are lost. The btn mutation thus specifically eliminates the DM cells, and this genetic ablation in turn reveals a requirement for DM cells as cellular cues for axonal guidance during transverse nerve outgrowth and bifurcation of the median nerve.
The comparison of gene expression patterns in a number of insect and crustacean species has led to some insight into the evolution of arthropod patterning mechanisms. These studies have revealed the fundamental nature of the parasegment in a number of organisms, shown that segments can be generated sequentially at the molecular level, and suggested that pair-rule pre-patterning might not be shared by all insects.
A monoclonal antibody (mAb 4D9) was used to analyze engrailed expression in amphipod embryos. As in other arthropods, engrailed is expressed in iterated transverse stripes in the germ band. In the anterior region these stripes are generated without a recognizable division pattern, and their appearance and formation show some irregularities. In the posterior region of the germ band, engrailed expression is correlated with a stereotyped cell division pattern resulting in a highly ordered formation and array of stripes. The engrailed positive cells mark the anterior border of genealogical units, which therefore can be compared with parasegments in Drosophila. Expression starts in the mandibular segment and proceeds first anteriorly and subsequently in a posterior direction. Initial stripes are one cell wide. The widening of stripes is caused by both division of engrailed positive cells and recruitment of new cells that did not previously express engrailed. The widening process is related to segment formation as the intersegmental furrows are established behind the engrailed expressing cells, which are restricted to the posterior portion of the forming segments. A comparison of the modes of engrailed expression in different segments suggests that initial engrailed expression is independent of a certain cell lineage or division pattern. The comparison of the development of the early engrailed stripes in different insects and crustaceans reveals some similarities which show that early engrailed expression is not necessarily clonally inherited.
The segment-polarity class of segmentation genes in Drosophila are primarily involved in the specification of sub-segmental units. In addition, some of the segment-polarity genes have been shown to specify cell fates within the central nervous system. One of these loci, gooseberry, consists of two divergently transcribed genes, gooseberry and gooseberry neuro, which share a paired box as well as a paired-type homebox. Here, the expression patterns of the two gooseberry gene products are described in detail. The gooseberry protein appears in a characteristic segment-polarity pattern of stripes at gastrulation and persists until head involution. It is initially restricted to the ectodermal and neuroectodermal germ layer, but is later detected in mesodermal and neuronal cells as well. The gooseberry neuro protein first appears during germ band extension in cells of the central nervous system and also, much later, in epidermal stripes and in a small number of muscle cells. P-element-mediated transformation with the gooseberry gene has been used to demonstrate that gooseberry transactivates gooseberry neuro and is sufficient to rescue the gooseberry cuticular phenotype in the absence of gooseberry neuro.
The development of Drosophila is typical of the so-called long germband mode of insect development, in which the pattern of segments is established by the end of the blastoderm stage. Short germband insects, such as the grasshopper Schistocerca americana, by contrast, generate all or most of their metameric pattern after the blastoderm stage by the sequential addition of segments during caudal elongation. This difference is discernible at the molecular level in the pattern of initiation of the segment polarity gene engrailed, and the homeotic gene abdominal-A (ref. 5). For example, in both types of insects, engrailed is expressed by the highly conserved germband stage in a pattern of regularly spaced stripes, one stripe per segment. In Drosophila, the complete pattern is visible by the end of the blastoderm stage, although engrailed appears initially in alternate segments in a pair-rule pattern that reflects its known control by pair-rule genes such as even-skipped. In contrast, in the grasshopper, the engrailed stripes appear one at a time after the blastoderm stage as the embryo elongates. To address the molecular basis for this difference, we have cloned the grasshopper homologue of the Drosophila pair-rule gene even-skipped and show that it does not serve a pair-rule function in early development, although it does have a similar function in both insects during neurogenesis later in development.
Monoclonal antibody 6F8 was used to characterize and clone fasciclin IV, a new axonal glycoprotein in the grasshopper, and to study its function during growth cone guidance. Fasciclin IV is dynamically expressed on a subset of axon pathways in the developing CNS and on circumferential bands of epithelial cells in developing limb buds. One of these bands corresponds to the location where the growth cones of the Ti1 pioneer neurons make a characteristic turn while extending toward the CNS. Embryos cultured in the 6F8 antibody or Fab exhibit aberrant formation of this axon pathway. cDNA sequence analysis suggests that fasciclin IV has a signal sequence; long extracellular, transmembrane, and short cytoplasmic domains; and shows no homology with any protein in the available data bases. Thus, fasciclin IV appears to be a novel integral membrane protein that functions in growth cone guidance.