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Biomedical subjects

J E Shaw

Publications and source records attributed to J E Shaw.

At least 55 records · Page 3Linked to original sources

Gustatory sweating in diabetes mellitus.

Gustatory sweating has been only rarely reported in diabetes mellitus and is thought to be due to axonal regeneration within the autonomic nervous system. We investigated the relationship of gustatory sweating to other diabetic complications. 196 patients in four groups (diabetic nephropathy, diabetic neuropathy, diabetic controls, and non-diabetic renal failure) were questioned about gustatory sweating. Somatic and autonomic neuropathy were assessed by clinical signs, vibration perception threshold, and heart rate variability. Sixty-nine percent of patients with nephropathy and 36% of those with neuropathy reported gustatory sweating, whereas less than 5% reported it in the other two groups. Five subjects reported that gustatory sweating either disappeared or significantly improved immediately after renal transplantation. Analysis of the nephropathy and neuropathy groups separately showed a strong correlation between gustatory sweating and degree of neuropathy (p < 0.01). This study shows that gustatory sweating is much more common than previously believed and demonstrates that it is often very closely linked with diabetic nephropathy.

Analysis of Variance↗

eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling.

The Drosophila melanogaster genes Passover and l(1)ogre and the Caenorhabditis elegans gene unc-7 define a gene family whose function is not known. We have isolated and characterized the C. elegans gene eat-5, which is required for synchronized pharyngeal muscle contractions, and find that it is a new member of this family. Simultaneous electrical and video recordings reveal that in eat-5 mutants, action potentials of muscles in the anterior and posterior pharynx are unsynchronized. Injection of carboxyfluorescein into muscles of the posterior pharynx demonstrates that all pharyngeal muscles are dye-coupled in wild-type animals; in eat-5 mutants, however, muscles of the anterior pharynx are no longer dye-coupled to posterior pharyngeal muscles. We show that a gene fusion of eat-5 to the green fluorescent protein is expressed in pharyngeal muscles. unc-7 and eat-5 are two of at least sixteen members of this family in C. elegans as determined by database searches and PCR-based screens. The amino acid sequences of five of these members in C. elegans have been deduced from cDNA sequences. Polypeptides of the family are predicted to have four transmembrane domains with cytoplasmic amino and carboxyl termini. We have constructed fusions of one of these polypeptides with beta-galactosidase and with green fluorescent protein. The fusion proteins appear to be localized in a punctate pattern at or near plasma membranes. We speculate that this gene family is required for the formation of gap junctions.

Action Potentials↗

Cancer prevention knowledge, attitudes, and clinical practice of nurse practitioners in local public health departments in North Carolina.

This study discusses the findings from a survey of the knowledge, attitudes, and clinical practice regarding cancer prevention and early detection of 101 nurse practitioners (NPs) working in the 87 county public health departments in North Carolina. Results show that nurse practitioners provide breast and cervical cancer screening services for most women over age 40 but are less likely to provide other types of cancer prevention, such as smoking cessation counseling or education about diet and cancer. NPs tended to rate their clinical skills in providing cancer screening as excellent but rate their skills in educating clients about cancer risk lower. Most NPs were interested in practice related to cancer control, especially learning more about the latest recommendations on cancer. However, in this study they indicated the least interest in learning more about smoking cessation methods or cancer prevention issues for men. These findings suggest that NPs in public health need further education and skills training related to cancer control, in addition to breast and cervical cancer screening.

Adult↗

The mec-8 gene of C. elegans encodes a protein with two RNA recognition motifs and regulates alternative splicing of unc-52 transcripts.

Mutations in the mec-8 gene of Caenorhabditis elegans were previously shown to affect the functions of body wall muscle and mechanosensory and chemosensory neurons. Mutations in mec-8 also strongly enhance the mutant phenotype of specific mutations in unc-52, a gene that encodes, via alternative splicing of pre-mRNA, a set of basement membrane proteins, homologs of perlecan, that are important for body wall muscle assembly and attachment to basement membrane, hypodermis and cuticle. We have cloned mec-8 and found that it encodes a protein with two RNA recognition motifs, characteristic of RNA binding proteins. We have used reverse transcription-PCR and RNase protection experiments to show that mec-8 regulates the accumulation of a specific subset of alternatively spliced unc-52 transcripts. We have also shown with antibodies to UNC-52 that mec-8 affects the abundance of a subset of UNC-52 isoforms. We propose that mec-8 encodes a trans-acting factor that regulates the alternative splicing of the pre-mRNA of unc-52 and one or more additional genes that affect mechanosensory and chemosensory neuron function.

Alternative Splicing↗

Management of foot problems in diabetes.

Many diabetic foot complications are preventable. This requires a team approach, aiming to identify the high-risk patient and provide appropriate education and foot care. An established ulcer needs careful management with the emphasis on pressure relief and establishing a good blood supply.

Combined Modality Therapy↗

Proton beams.

Explore the source record for details and available documents.

Humans↗

The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously.

Mutations in the C. elegans gene lin-44 lead to reversals in the polarity of certain asymmetric cell divisions. We have discovered that lin-44 is a member of the Wnt family of genes, which encode secretory glycoproteins implicated in intercellular signaling. Both in situ hybridization experiments using lin-44 transcripts and experiments using reporter constructs designed to mimic patterns of lin-44 expression indicate that lin-44 is expressed in hypodermal cells at the tip of the tail and posterior to the cells with polarities affected by lin-44 mutations. Our mosaic analysis indicates that lin-44 acts cell nonautonomously. We propose that LIN-44 protein is secreted by tail hypodermal cells and affects the polarity of asymmetric cell divisions that occur more anteriorly in the tail.

Amino Acid Sequence↗

The achievement of isoeffective bronchial mucosal dose during endobronchial brachytherapy.

PURPOSE: The use of endobronchial brachytherapy in the treatment of lung cancer is increasing due to the more widespread availability of high dose rate afterloading equipment. The complications include small airway (segmental and small lobar bronchi) fibrosis, stenosis, and obstructive complications in addition to hemorrhage. A progressive reduction in the diameter of the bronchial lumen occurs at each division of the bronchial tree. If uniform dwell times along a bronchial catheter treatment length are used, this will result in higher doses being given to the bronchial mucosa in the distal part of the treatment volume where the brachytherapy source mucosa distances are smaller, and underdosage proximally, where the source mucosa distances are larger. METHODS AND MATERIALS: The known mathematical relationships of the sequential reductions in the diameter of the bronchial lumen have been incorporated into two methods of optimization, which have been compared to uniform dwell times along a treatment length from trachea to segmental bronchus. RESULTS: The resulting isodose plots are presented, and demonstrate the extent of the overdosage distally, and the underdosage proximally when using uniform dwell times, and the achievement of isoeffective mucosal doses when using differential dwell times. CONCLUSION: This refinement in brachytherapy technique offers the potential for reduced normal tissue complications and possibly improved tumor control by reducing overdosage and underdosage, respectively.

Brachytherapy↗

A Caenorhabditis elegans act-4::lacZ fusion: use as a transformation marker and analysis of tissue-specific expression.

A plasmid vector that serves as a dominant marker for isolating transformed animals in Caenorhabditis elegans has been constructed as a translational fusion of the C. elegans act-4 gene (encoding actin) and the Escherichia coli lacZ gene. This gene fusion can be used as a marker in transformation rescue experiments in any fertile strain of C. elegans. Progeny of animals injected with the act-4::lacZ fusion vector are stained histochemically with XGal, and transformants turn blue. The internal eggs of stained animals remain viable, allowing recovery of the transformed strain. When the act-4::lacZ vector is co-injected with an unselected plasmid with which it shares some sequence homology, most transformants that are recovered by screening for expression of the act-4::lacZ fusion contain both plasmids. Production of active beta Gal in animals transformed with the act-4::lacZ gene fusions appears to be limited to certain tissues. A chimeric gene that contains the 5' and 3' regions of act-4 is expressed strongly in the body-wall muscles, vulval muscles, and spermathecae. Addition of the internal portion of act-4, including the protein-coding region and introns, to this chimeric gene leads to additional lacZ expression in the pharynx.

Actins↗

A variant Tc4 transposable element in the nematode C. elegans could encode a novel protein.

A variant C. elegans Tc4 transposable element, Tc4-rh1030, has been sequenced and is 3483 bp long. The Tc4 element that had been analyzed previously is 1605 bp long, consists of two 774-bp nearly perfect inverted terminal repeats connected by a 57-bp loop, and lacks significant open reading frames. In Tc4-rh1030, by comparison, a 2343-bp novel sequence is present in place of a 477-bp segment in one of the inverted repeats. The novel sequence of Tc4-rh1030 is present about five times per haploid genome and is invariably associated with Tc4 elements; we have used the designation Tc4v to denote this variant subfamily of Tc4 elements. Sequence analysis of three cDNA clones suggests that a Tc4v element contains at least five exons that could encode a novel basic protein of 537 amino acid residues. On northern blots, a 1.6-kb Tc4v-specific transcript was detected in the mutator strain TR679 but not in the wild-type strain N2; Tc4 elements are known to transpose in TR679 but appear to be quiescent in N2. We have analyzed transcripts produced by an unc-33 gene that has the Tc4-rh1030 insertional mutation in its transcribed region; all or almost all of the Tc4v sequence is frequently spliced out of the mutant unc-33 transcripts, sometimes by means of non-consensus splice acceptor sites.

Amino Acid Sequence↗

Molecular and genetic analysis of unc-7, a Caenorhabditis elegans gene required for coordinated locomotion.

Mutations in the Caenorhabditis elegans gene unc-7 confer an uncoordinated phenotype. Wild-type animals trace smooth, sinuous waves as they move; unc-7 mutants make irregular bends or kinks along their bodies, particularly when they move forward. The unc-7 locus has also been implicated in the nematode's response to volatile anesthetics. We have cloned unc-7 by transposon tagging: an unc-7 mutation was correlated with the insertion of the transposon Tc1, and reversion of the mutant phenotype was correlated with loss of the Tc1 element. We have physically mapped the region flanking the sites of Tc1 insertion and identified DNA rearrangements corresponding to eight additional unc-7 alleles. Northern analysis indicates that a 2.7-kb unc-7 message is present in all developmental stages but is most abundant in L1-L3 larvae. The 5' end of the message contains a trans-spliced leader SL1. An 18-kb intron is located upstream of the predicted translational start site of the gene, and DNA breakpoints of four gamma-ray-induced alleles were located within this intron. We determined the sequence of a cDNA corresponding to the unc-7 message. The message may encode a 60-kd protein whose amino acid sequence is unrelated to any other available protein sequence; a transmembrane location for the unc-7 protein is predicted. We predict from our analysis of unc-7 genetic mosaics that the unc-7 gene product is not required in muscle cells for wild-type coordination but is probably required in motor neurons (although a hypodermal role has not been excluded). We speculate that unc-7 may be involved in the function of neuronal ion channels.

Alleles↗

Growth hormone expression in human Burkitt lymphoma serum-free Ramos cell line.

A human nonpituitary cell line grown under serum-free (sf) conditions (sfRamos Burkitt lymphoma cell line) has been reported to secrete a 29K PRL-like peptide which acts as an autocrine growth factor. Conditioned medium from these cells was examined for lactogenic activity using the Nb2 bioassay and RIAs specific for human GH (hGH) and hPRL. SfRamos conditioned medium stimulated the growth of Nb2 cells. Anti-hGH monoclonal antibodies but not anti-hPRL inhibited the mitogenic effect of sfRamos conditioned medium on Nb2 cells. Immunoreactive hGH but not hPRL was detected by RIA. Immunoprecipitation with anti-hGH polyclonal antibody followed by Western blot analysis with anti-hGH monoclonal antibody revealed a specific 22K band with the same mobility as pituitary hGH. Northern blot analysis with an hGH complementary DNA (cDNA) probe revealed a 1.0-kilobase transcript migrating coincident with pituitary hGH messenger RNA. A less abundant, 1.6-kilobase transcript was also observed. Reverse transcriptase-polymerase chain reaction using specific primers for the hGH cDNA generated the predicted 248-base pair band. Polymerase chain reaction sequencing of this fragment revealed sequence identity to the hGH-N cDNA, demonstrating conclusively the expression of the hGH-N gene in the sfRamos cell line.

Antibodies↗

Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene unc-33.

Mutations in the unc-33 gene of the nematode Caenorhabditis elegans lead to severely uncoordinated movement, abnormalities in the guidance and outgrowth of the axons of many neurons, and a superabundance of microtubules in neuronal processes. We have cloned unc-33 by tagging the gene with the transposable element Tc4. Three unc-33 messages, which are transcribed from a genomic region of at least 10 kb, were identified and characterized. The three messages have common 3' ends and identical reading frames. The largest (3.8-kb) message consists of the 22-nucleotide trans-spliced leader SL1 and 10 exons (I-X); the intermediate-size (3.3-kb) message begins with SL1 spliced to the 5' end of exon V and includes exons V-X; and the smallest (2.8-kb) message begins within exon VII and also includes exons VIII-X. A gamma-ray-induced deletion mutation situated within exon VIII reduces the sizes of all three messages by 0.5 kb. The three putative polypeptides encoded by the three messages overlap in C-terminal sequence but differ by the positions at which their N termini begin; none has significant similarity to any other known protein. A Tc4 insertion in exon VII leads to alterations in splicing that result in three approximately wild-type-size messages: the Tc4 sequence and 28 additional nucleotides are spliced out of the two larger messages; the Tc4 sequence is trans-spliced off the smallest message such that SL1 is added 13 nucleotides upstream of the normal 5' end of the smallest message.

Amino Acid Sequence↗

Production of immunoreactive forms of growth hormone by the Burkitt tumor serum-free cell line sfRamos.

Tumor B-cell mitogenesis may be regulated by autocrine secretions that cross-react immunologically with neuroendocrine peptides. This hypothesis is supported by our recent report that immunoreactive human PRL (ir-hPRL) is produced by and required for the continuous growth of sfRamos, a Burkitt tumor serum-free cell line. Further support for the hypothesis is provided in this study. The data illustrate that antiserum immunoglobulin fraction G (IgG) to synthetic human GH (NIDDK anti-synth hGH IC-4), but not nonimmune serum IgG, completely inhibited sfRamos proliferation. In addition, anti-synth hGH, but not nonimmune serum, identified several polypeptides in sfRamos spent medium that were not in serum-free control medium, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions and the Western immunoblot procedure. The ir-hGH polypeptides were in the 35- to more than 300-kilodalton (kDa) range, with a 48-kDa polypeptide as a major component. A polypeptide with electrophoretic properties identical to those of the hGH monomer (22 kDa) was not detected, even with prior incubation of spent medium with N-ethylmaleimide and dithiothreitol. Pituitary preparations of hPRL and hGH, each with the monomer form as the major component, were neither mitogenic for growth-arrested cells nor did they synergize with spent medium to enhance growth, either alone or in combination, whereas spent medium with immunoreactive polypeptides larger than the monomer form markedly stimulated proliferation of growth-arrested cells. These findings demonstrate that sfRamos mitogenesis is potentially regulated by autocrine secretions with cross-immunoreactivity to two anterior pituitary hormones.

Blotting, Western↗