[Urine alcohol determination].
Explore the source record for details and available documents.
Ethanol↗
Biomedical subjects
R Werner
Publications and source records attributed to R Werner.
Pyrogenicity of etiocholanolone and interleukin-1 in New and Old World Monkeys.
Etiocholanolone (5beta-androstan-3alpha-ol-17-one; designated E) is one of the major products of metabolism of testosterone and androstenedione (androst-4-ene-3,17-dione) in many mammalian species, including humans. E and several other 5beta-reduced steroids have been found to induce fever in humans. The pyrogenic effect of these steroids has been shown to be due to the release of interleukin-1 (IL-1) from the leukocytes that are mobilized in response to the steroid injections. Old World Monkeys such as Rhesus monkeys (Macaca mu/atta), metabolize androgens similarly to humans, and E is a normal metabolite. However, New World Monkeys such as Squirrel monkeys (Saimiri sciureus), lack hepatic 5alpha- and 5beta-steroid reductases and excrete androgens primarily in an unaltered state; E is not produced. Therefore, we postulate that Squirrel monkeys likewise may have lost the ability to respond to 17-ketosteroids such as E. To test this hypothesis, adult male Rhesus and Squirrel monkeys were treated with E, and their rectal temperatures were recorded over a 24-hr period. Rhesus monkeys exhibited a rise of up to 3 degrees F following E injection. Squirrel monkeys, on the other hand, did not exhibit any increase in rectal temperature over the 24-hr period, even when doses up to 250 times the effective human dose were used. However, both species responded to injected IL-1alpha with a robust increase in rectal temperature. The data show that E is pyrogenic in Rhesus, but not Squirrel monkeys. The findings support the notion that injected E may induce release of IL-1 in Rhesus monkeys, but not in Squirrel monkeys.
Androsterone↗
Mutation in the nerve-specific 5'non-coding region of Cx32 gene and absence of specific mRNA in a CMTX1 Italian family. Mutations in brief no. 195. Online.
Charcot-Marie-Tooth type I demyelinating neuropathies are genetically heterogeneous disorders (chrmosome 17,1,X). There are at least three genes on X chromosome, the more frequently involved being Cx32 in Xq13.1. Cx32 encodes for connexin-32, a gap junction protein of 283 aminoacids. We report the results of molecular studies in a CMTX1 Italian family, in which the mutation, found in the 5'-UTR, resulted in an abnormal mRNA connexin-32 expression. Mutations in PMP22 and P0 genes were also excluded in this family. Cx32 gene analysis carried out by PCR-SSCP on family members genomic DNAs, running a 321 bp fragment spanning the TATA box, the trasciptional start site, and the non coding exon 1b, revealed a shift correlated with a transition from C to T at position 40 of exon 1b of the 12 affected members, while was not found in the controls. Then the RT PCR-SSCP on cDNA from two peripheral nerve biopsies of two heterozygous females of the family were sequenced showing only the wild-type alleles and suggesting that mutated mRNAs were too unstable to be detected. The result also suggests a regulating role of the 5'-UTR of Cx32 mRNA.
5' Untranslated Regions↗
Cooperative problem solving with personal mobile information tools in hospitals.
Health-care professionals have a broad range of needs for information and cooperation while working at different points of care (e.g., outpatient departments, wards, and functional units such as operating theaters). Patient-related data and medical knowledge have to be widely available to support high-quality patient care. Furthermore, due to the increased specialization of health-care professionals, efficient collaboration is required. Personal mobile information tools have a considerable potential to realize almost ubiquitous information and collaborative support. They enable to unite the functionality of conventional tools such as paper forms, dictating machines, and pagers into one tool. Moreover, they can extend the support already provided by clinical workstations. An approach is described for the integration of mobile information tools with heterogeneous hospital information systems. This approach includes identification of functions which should be provided on mobile tools. Major functions are the presentation of medical records and reports, electronic mailing to support interpersonal communication, and the provision of editors for structured clinical documentation. To realize those functions on mobile tools, we propose a document-based client-server architecture that enables mobile information tools to interoperate with existing computer-based application systems. Open application systems and powerful, partially wireless, hospital-wide networks are the prerequisites for the introduction of mobile information tools.
Decision Making, Computer-Assisted↗
A chimeric connexin forming gap junction hemichannels.
Connexins are the subunits of gap junction channels which connect neighboring cells. With the exception of lens connexins, they usually do not form open hemichannels in the cell membrane of single cells. Here we describe a chimeric connexin consisting of cx32 where the first extracellular loop sequence is replaced by the corresponding cx43 sequence. This chimera, cx32E143, forms conventional gap junction channels in the paired oocyte assay. In addition cx32E143 induces a membrane conductance in single oocytes. This membrane conductance is voltage dependent and is similarly sensitive to CO2 as are gap junction channels formed by the chimera or by wild-type cx32. These data suggest that cx32E143 forms patent hemichannels in the plasma membrane of single oocytes. This conclusion is further supported by the observation that oocytes expressing cx32E143 take up from the bath medium tracer molecules known to pass through gap junction channels.
Animals↗
Identification of a pore lining segment in gap junction hemichannels.
The ability of certain connexins to form open hemichannels has been exploited to study the pore structure of gap junction (hemi)channels. Cysteine scanning mutagenesis was applied to cx46 and to a chimeric connexin, cx32E(1)43, which both form patent hemichannels when expressed in Xenopus oocytes. The thiol reagent maleimido-butyryl-biocytin was used to probe 12 cysteine replacement mutants in the first transmembrane segment and two in the amino-terminal segment. Maleimido-butyryl-biocytin was found to inhibit channel activity with cysteines in two equivalent positions in both connexins: I33C and M34C in cx32E(1)43 and I34C and L35C in cx46. These two positions in the first transmembrane segment are thus accessible from the extracellular space and consequently appear to contribute to the pore lining. The data also suggest that the pore structure is complex and may involve more than one transmembrane segment.
Amino Acid Sequence↗
Intracarpal canal pressures: the role of finger, hand, wrist and forearm position.
OBJECTIVE: The study examined the change in intracarpal canal pressure (ICCP) in relationship to finger, hand, wrist and forearm position. DESIGN: The study was an in vivo measurement of ICCP in seven subjects undergoing a standardized set of manoeuvres that systematically varied finger, hand, wrist, and forearm position. BACKGROUND: It has been known that the ICCP increased with extremes of wrist flexion and extension but the change in pressure in response to radial and ulnar deviation as well as hand and forearm position has not been reported. METHODS: The ICCP was measured using a slit catheter technique; each variation of position was repeated three times with continuous monitoring of ICCP, wrist angulation, and metacarpal-phalangeal joint angulation. RESULTS: The study demonstrated that ICCPs were lowest when the wrist is in a neutral position, the hand relaxed with fingers flexed and the forearm in a semi-pronated position. Wrist extension and flexion resulted in the greatest increase in ICCP followed by forearm pronation and supination. Radial and ulnar deviation also increased the pressure but to a lesser extent. CONCLUSIONS: The findings of this study support the concept that the wrist and forearm should be maintained in a neutral position during vocational and avocational activities in an effort to minimize pressure within the carpal tunnel and thereby reduce the risk of developing carpal-tunnel syndrome. RELEVANCE: It is desirable to know how the ICCP changes in response to change in hand, wrist, and forearm position so that work activities are designed to minimize the pressure within the carpal canal and thus maintain the viability of the median nerve within the carpal canal.
Journal Article↗
Detection and tissue distribution of potato spindle tuber viroid in infected tomato plants by tissue print hybridization.
Potato spindle tuber viroid (PSTVd) was detected in two cultivars of tomato (Lycopersicon esculentum Mill.) by tissue print hybridization of cross-sections of stem and rhachis, using a 35S-labeled PSTVd RNA probe. PSTVd was detectable in the viroid-sensitive and symptom-developing cv "Rutgers" 2 weeks p.i., and in the viroid-tolerant and practically symptomless cv "Goldkugel" 3 weeks p.i. In both tomato cultivars, PSTVd accumulated in the upper parts of the plants newly grown after inoculation. It was predominantly found in association with the ring formed by the vascular tissue. The final accumulation of PSTVd as well as its spatial distribution were similar in the sensitive and in the tolerant tomato cultivar, as estimated from the tissue print autoradiographs. Thus, tissue print hybridization provides a rapid and sensitive means for viroid diagnosis and for the assessment of tissue-specific localization of the viroid RNA.
Autoradiography↗
A role for an inhibitory connexin in testis?
Functional expression of gap junction proteins can be obtained conveniently with the paired oocyte cell--cell channel assay. So far all gap junction proteins (connexins), with the exception of one, have been found to make functional channels either by themselves or as hybrid channels (two hemichannels of different connexin composition). Connexin33 (cx33) appears not to follow this rule. Expression of cx33 in oocytes does not yield functional channels, and attempts to identify another connexin with which cx33 can form hybrid channels have failed so far. The observation was made that cx33 inhibits functional expression of other connexins in a connexin-specific way. While expression of cx32 remains unaffected by coinjection into oocytes of cx33 mRNA together with cx32 mRNA, junctional conductance obtained with cx43 is marginally reduced whereas coinjection of cx33 mRNA at equimolar concentrations almost completely abolishes functional cx37 expression. The fact that testis is the only tissue found to express significant levels of cx33 mRNA together with cx37 and cx43 suggests a possible functional role for an inhibitory connexin. A model is proposed where cx33 limits a cell's capability to make functional channels by allowing formation of heterotypic channels with other cells while formation of homotypic channels is disallowed. Such a mechanism would permit asynchronous maturation of germ cells while at the same time allowing communication between germ cells and Sertoli cells.
Animals↗
The human connexin32 gene is transcribed from two tissue-specific promoters.
The connexin32 (cx32) gene codes for the gap junction protein found in liver, pancreas and nervous tissue. Recently mutations in the coding region of this gene have been associated with the dominant X-linked form of Charcot-Marie-Tooth (CMTX1) neuropathy. Since some CMTX1 patients show no mutations in their cx32 gene coding region, it was speculated that these patients carry mutations in the promoter region of the gene. This paper describes the organization of the human cx32 gene and its tissue-specific transcription. The gene consists of three exons that are alternatively spliced to produce mRNAs with different 5'-untranslated regions (UTRs). Transcription is initiated from two tissue-specific promoters. In liver and pancreas, promoter P1, located more than 8 kb upstream of the translation start codon, is used, and the transcript is processed to remove a large intron. In contrast, in nerve cells, transcription is initiated from promoter P2, located 497 bp upstream from the translation start codon, and the transcript is processed to remove a small 355-pb intron. The downstream exon, which includes the entire coding sequence, is shared by both mRNAs. CMTX1 patients with a normal cx32 coding region are expected to have mutations in this newly described promoter P2 rather than the known promoter P1.
Alternative Splicing↗
Mutations of the noncoding region of the connexin32 gene in X-linked dominant Charcot-Marie-Tooth neuropathy.
We studied two families with X-linked dominant Charcot-Marie-Tooth neuropathy. The clinical findings included onset around age 14 years, with moderate weakness of feet extensors and palmar and dorsal interossei, areflexia, distal hypesthesia, and slow progressivity. Motor nerve conduction velocities showed slowing (20 to 30 m/sec) and EMGs were normal. Genetic linkage analysis revealed positive lod scores with the markers of the Xq13.1 region in family 2, but was noninformative in family 1. There were no point mutations in the connexin32 gene coding region. Instead, family 1 revealed a T-to-G transversion at position -528 relative to the ATG start codon, whereas family 2 showed a C-to-T transition at position -458. The first mutation is located in the nerve-specific connexin32 promoter just upstream of the transcription start site, the second is located in the 5' untranslated region of the mRNA.
Adult↗
Use of alternate promoters for tissue-specific expression of the gene coding for connexin32.
The promoter of rat connexin32 (Cx32), the gap junction protein found in liver, was studied in transgenic mice. Cx32 transgenes, containing 2.5-kb of sequence upstream from the promoter, exon I, the entire 6.1-kb intron and the beginning of the coding sequence linked to the gene encoding luciferase (Luc), were found to be expressed in mouse in the same tissue-specific manner as previously reported for Cx32. Another construct lacking the promoter, but retaining 1.8 kb from the 3' end of the intron, was found to be expressed specifically in the nervous system. This result suggested that a second promoter, different from that used in liver, functions in nervous tissue. The use of this promoter in normal rats was corroborated by sequence analysis of reverse-transcribed PCR products obtained from rat nervous tissue RNA. The second promoter drives the synthesis of a second Cx32 mRNA species that is processed to remove a small 345-bp intron that shares its acceptor splice site with the large intron. This finding could have implications for the genetic basis of the X-linked form of Charcot-Marie-Tooth disease (CMT-X) in those patients that do not exhibit mutations in the Cx32-coding region.
Animals↗
Isolation of viroid-RNA-binding proteins from an expression library with nonradioactive-labeled RNA probes.
The detection and isolation of cDNAs of tomato proteins that are able to bind to viroid RNA molecules are described. They were found by screening of a lambda gt11 cDNA expression library using a modification of the previously established ligand-blotting procedure to detect DNA- and RNA-binding proteins. The essentials of our modifications are the use of (i) digoxigenin-labeled viroid RNA, (ii) low concentration of the labeled probes and (iii) an expression library that allows the direct isolation of cDNA clones. The analysis of various isolated clones showed that this method is reliable for RNA-ligand screening and North-Western blotting. Applied to viroid RNA, these experimental tools provide the precondition for further studies on the specificity of the isolated proteins.
Gene Library↗
An integrated approach for mobile information processing in hospitals.
Computer-based mobile information processing in hospitals is at a turning point of becoming a substantial and integral part of hospital information systems. Its necessity and potential require a comprehensive systematic approach to support the needs of health care professionals and thus to contribute to high quality patient care and medical research. From the authors' point of view, standardized digital documents could become an appropriate basis for distributed mobile information processing in hospitals. An architecture for the integrated co-operative use of conventional, stationary, and mobile information tools is a major research topic at Heidelberg University. The objective of this paper is to present a departmental prototype design to establish mobile information processing as an integral part of hospital information systems through the use of standardized digital documents.
Computer Communication Networks↗
[Lymph drainage routes and variability in preoperative efferent lymph flow scintigraphy in malignant melanoma of the trunk].
Malignant melanoma of the skin has become a real problem due to the increasing number of cases. No other tumor is induced by long term UV-radiation of the skin. Excision of the primary tumor is the treatment of choice in this disease. Before excision of the tumor lymphoscintigraphy is the first choice in diagnosis to demonstrate the draining lymph vessels and lymph node groups of an malignant melanoma for later operation. This work current the status quo of lymphoscintigraphy in malignant melanoma of the trunk.
Adult↗
A connexin-32 mutation associated with Charcot-Marie-Tooth disease does not affect channel formation in oocytes.
Members of the connexin family differ most in their carboxy-termini, both with respect to sequence and length. In order to assess the contribution of this region to channel function, a series of carboxy-terminal deletion mutants were tested in the paired-oocyte expression system. Connexin-32 can be truncated by 64 amino acids without detectable loss of its known channel properties. Removal of additional amino acids results in a progressive loss of function over a stretch of 4 amino acids. In addition to this effect of length the charge of the carboxy-terminus appears to be another determinant of channel function. One of the fully functional deletion mutants, carrying a stop codon after amino acid-219, had been reported to be associated with Charcot-Marie-Tooth disease. The implications of this finding are discussed.
Amino Acid Sequence↗
The connexin43 gene is responsive to oestrogen.
Connexin43 is the major protein of gap junctions in heart and smooth muscle including the myometrium. Molecular cloning of the connexin43 gene reveals a similar organization to that exhibited by other connexin genes: the 5' untranslated region is interrupted by an 8.5 kilobase intron. The promoter region preceding the first exon contains a TATA box and AP-1 and AP-2 sites. In addition, a series of half-palindromic oestrogen response elements is present in this region. When this promoter is linked to the reporter gene luciferase, it drives the expression of luciferase constitutively in HeLa cells transfected with this luciferase-connexin43 promoter fusion construct. When the same cells are cotransfected with oestrogen receptor cDNA, an upregulation of luciferase expression by oestrogen occurs in a cell-specific manner.
Animals↗
Attempts to define functional domains of gap junction proteins with synthetic peptides.
To map the binding sites involved in channel formation, synthetic peptides representing sequences of connexin 32 were tested for their ability to inhibit cell-cell channel formation. Both large peptides representing most of the two presumed extracellular loops of connexin32 and shorter peptides representing subsets of these larger peptides were found to inhibit cell-cell channel formation. The properties of the peptide inhibition suggested that the binding site is complex, involving several segments of both extracellular loops. One of the peptides (a 12-mer) did not inhibit but instead was found to form channels in membranes. Both in oocyte membranes and in bilayers, the channels formed by the peptide were asymmetrically voltage dependent. Their unit conductances ranged from 20 to 160 pS. These data are discussed in the form of a model in which the connexin sequence represented by the peptide is part of a beta structure providing the lining of the channel pore.
Amino Acid Sequence↗