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An evaluation of the Israeli Sexual Assault Evidence Collection Kit and additional exhibits in casework.

A Sexual Assault Evidence Collection Kit is a well known device used by several countries, including Israel. Sexual offence cases containing kits and additional exhibits are brought to the Forensic Biology Laboratory of the Israeli Police. For the purpose of this work, the kits and the exhibits were evaluated for their value as evidence. It was found that the additional exhibits had some advantage over the kit. On the other hand, the kit had its own advantage and therefore a proper forensic case should include the kit and the additional exhibits.

Forensic Medicine↗

Adrenodoxin with a COOH-terminal deletion (des 116-128) exhibits enhanced activity.

Adrenodoxin, purified from bovine adrenal cortex, was subjected to trypsin cleavage to yield a trypsin-resistant form, designated TT-adrenodoxin. Sequencing with carboxypeptidase Y identified the trypsin cleavage site as Arg-115, while Edman degradation indicated no NH2-terminal cleavage. Native adrenodoxin and TT-adrenodoxin exhibited similar affinity for adrenodoxin reductase as determined in cytochrome c reductase assays. In side chain cleavage assays using cytochrome P-450scc, however, TT-adrenodoxin demonstrated greater activity than adrenodoxin with cholesterol, (22R)-22-hydroxycholesterol, or (20R,22R)-20,22-dihydroxycholesterol as substrate. This enhanced activity is due to increased affinity of TT-adrenodoxin for cytochrome P-450scc; TT-adrenodoxin exhibits a 3.8-fold lower apparent Km for the conversion of cholesterol to pregnenolone. TT-Adrenodoxin was also more effective in coupling with cytochrome P-450(11) beta, exhibiting a 3.5-fold lower apparent Km for the 11 beta-hydroxylation of deoxycorticosterone. In the presence of partially saturating cholesterol, TT-adrenodoxin elicited a type I spectral shift with cytochrome P-450scc similar to that induced by adrenodoxin, and spectral titrations showed that oxidized TT-adrenodoxin exhibited a 1.5-fold higher affinity for cytochrome P-450scc. These results establish that COOH-terminal residues 116-128 are not essential for the electron transfer activity of bovine adrenodoxin, and the differential effects of truncation at Arg-115 on interactions with adrenodoxin reductase and cytochromes P-450 suggest that the residues involved in the interactions are not identical.

Adrenodoxin↗

[A traveling exhibit: "Protecting the hands at work"].

Information is an important and even essential step in the prevention process. An exhibition, which traditionally favours a visual approach, is a way of providing information for the public at large. The exhibition, the first to be produced under the auspices of the Claude Verdan foundation, tackles the issue in a general way. The aim is to: make people aware and encourage prevention in the work environment; situate the hand in a preventive context; show the importance of the hand as a work-tool; present the quantitative and qualitative extent of diseases and accidents of the hand; make the interest and difficulties in collecting information known (especially about professional diseases and workers not affiliated to the CNA); stimulate continuing search of information about prevention in the work environment. The exhibition presents certain aspects of the history of prevention in the working world, Swiss institutions involved, notions of epidemiology of professional diseases and accidents of the hand (obtained from the CNA files), as well as different types of available prevention. The material used is light (posters, slides, video) and thus transportable, and so can be widely used for the people concerned at their place of work....

Accidents, Occupational↗

The staging of a hospice arts and crafts exhibition in the UK.

The use of arts in hospices is now well established. However, the voluntary nature of much hospice work in England encourages most regular creative activities to be provided by volunteers with minimal financial support. This article looks at how a successful arts and crafts exhibition for a hospice community was staged by a volunteer arts worker, helped by art and design students from the local university. It was not intended that the exhibition should be a research project; however, it became clear that to learn more about arts practice within a hospice environment, it would need to be appraised in some way. The project leader (and author) adopted an approach which reflected on the responses of people involved in the preparation and staging of the exhibition.

Art↗

Public health on the railroad: William Freeman Snow and the California Sanitation Exhibit.

This paper describes the California Sanitation Exhibit, a railroad car outfitted for instruction in public health that toured California in 1909 and 1910. The sanitation exhibit used display models, photographs, and lectures to educate the public about tuberculosis and other infectious diseases, waste contamination, and the dangers of bad milk. The success of the exhibit, which reached 5% of the state's population, resulted in the appointment of its creator, William Freeman Snow, as secretary of the California State Board of Health.

California↗

Disease and domesticity on display: the Montreal Tuberculosis Exhibition, 1908.

This article explores ideas about tuberculosis in early 20th-century Montreal by looking at one particular event: The Montreal Tuberculosis Exhibition of 1908. An analysis of the layout and design of this exhibition reveals that objects were manipulated to convey specific messages. Domestic spaces were showcased as being particularly troublesome. The exhibition suggested that the home was a potentially dangerous agent of disease, thereby revealing a relationship between disease and everyday life.

Communicable Disease Control↗

Permanent visual display exhibits. A supplementary instructional technique in critical care education.

The discipline of critical care is being challenged to provide ongoing education to the various groups of critical care health providers. Traditional modalities of instruction may not suffice as unique circumstances exist in the practice and daily delivery of patient care. These unique circumstances include a never-ending introduction of new devices, tubes, and catheters into practice. In addition, the intensive care setting features a wide variability of work experience, a high turnover rate of personnel, variable cognitive approaches to understanding technical devices, and a stressful workplace. In their surgical intensive care unit, the authors have developed a set of permanent visual display exhibits. These exhibits were designed to specifically address the above problems and serve as a supplementary mode of education for our diverse medical, nursing, and technical staff. The exhibits may provide an example for other intensive care units and educators.

Critical Care↗

Montreal Museum exhibit provides clear picture of advances in medical imaging.

An exhibit at the McCord Museum of Canadian History, which runs until November, marks the centennial of the discovery of the x-ray. Among the items on display are a portable field x-ray machine used during World War I and one of the machines commonly found in shoe stores between 1930 and 1950 to x-ray customers' feet. The exhibit also features one of the first scanners used in North America. Dr. Denis Melançon, a radiologist at the Montreal Neurological Institute, was the driving force behind the McCord exhibit. "I wanted to show [not only] the historical and scientific aspects of the discovery, but also its medical and social applications," he says.

Exhibitions as Topic↗

[Physicians facing Paracelsus. Final thoughts at an art exhibit for physicians in honor of the 500th anniversary of Paracelsus in Old Bad Pfäfers on 18 September 1993].

The symposium for physicians in the Old Bad Pfäfers in honor of the 500th anniversary of Paracelsus' was framed by an art-exhibition with art-works from eleven amateur artists. Nine physicians, one psychologist/psychotherapist and one nurse met for the exhibition in order to get involved intensively with the personality of the medical colleague, natural scientist and philosopher Theophrast von Hohenheim. New interpretations of this 'seltsam wunderlichen Mann aus Einsiedeln' and of the Taminaschlucht, the place where he stayed for a short while, were exhibited. The artists have briefly been introduced during the opening session. The importance of the 'imagination' and of the creative work of a physician are emphasized.

Exhibitions as Topic↗

Apoptosis in mycobacterium tuberculosis infection in mice exhibiting varied immunopathology.

This study examined mechanisms contributing to pulmonary immunopathology following acute Mycobacterium tuberculosis (MTB) infection in vivo in a murine model. A/J and C57BL/6 mice were intravenously infected with MTB (Erdman). Pathological differences were found between strains, unrelated to pulmonary load of bacilli. A/J mice developed progressive interstitial pneumonitis, while C57BL/6 mice maintained granuloma formation. The contribution of FAS and FAS ligand-mediated apoptosis was assessed via bioluminescent reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining, and TUNEL assessment of DNA fragmentation. Cytokine messages for pulmonary tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), as well as for the lytic molecules perforin and granzyme B, were quantified. Immunohistochemical staining for CD3 receptor was performed to monitor lymphocytic lung infiltration. Soon after infection, A/J mice exhibited increased pulmonary IFN-gamma message, concurrent with the appearance of CD3+ lymphocytes distributed throughout the lung. C57BL/6 mice exhibited perivascular cuffing, with no accompanying increase in IFN-gamma message. A/J mice also had elevated levels of FAS and FAS ligand message and protein early after infection, while the C57BL/6 mice had no increased expression of these molecules. Both strains exhibited qualitatively similar numbers of TUNEL-positive cells throughout infection, with a marked increase on day 7. Apoptotic cells appeared to co-localize with acid fast bacilli. It is therefore proposed that apoptosis during initial granuloma formation following MTB infection may occur through a FAS/FAS ligand-independent pathway. Moreover, a failure of completion of the FAS/FAS ligand-mediated apoptosis pathway in the A/J mice may contribute to inefficient elimination of lymphocytes, thus further aggravating pulmonary pathology.

Acute Disease↗

Isolation from a human MDR lung cell line of multiple clonal subpopulations which exhibit significantly different drug resistance.

The heterogeneous nature of an adriamycin-selected human MDR squamous lung cell line, DLKP-A, was investigated by isolating and characterising 9 of its clonal subpopulations. The DLKP-A cell line exhibits resistance to the classical MDR drugs, overexpresses P-glycoprotein and displays reduced topoisomerase II amounts. The clonal cell lines exhibit a wide range of resistance extents, with the most resistant clone displaying 9 times the extent of adriamycin resistance observed in the least resistant clone. A number of clones exhibit sensitivity to the concentration of adriamycin in which the parental cell line was selected, possibly indicating cooperation between the more and less resistant cells. Detailed analysis of 4 of the clonal subpopulations revealed broadly similar drug resistance mechanisms. Alterations in expression of the MDR-associated genes MDR1 and Topo IIalpha were observed, with no detectable changes in the expression of MDR3, MRP, GSTpi, Topo IIbeta, Topo I and CYP1A1 noted. However, each clonal cell line displayed a distinct extent of expression of MDR1 and Topo IIalpha and further characterisation of the clones indicated that other modes of drug resistance may exist in at least one of the cell lines. In particular, 2 of the clones (DLKPA6B and DLKPA11B) which have almost identical drug resistance profiles appear to have quite different mechanisms of resistance. The clonal subpopulations possess individual growth rates, amounts of adriamycin accumulation and susceptibility to toxicity-enhancement by MDR-modulating agents. It was possible to generate a cell line with a drug toxicity profile similar to DLKP-A by mixing some of the clonal subpopulations. Our results provide evidence of heterogeneity within an MDR human cell population with respect to resistance and expression of MDR-associated genes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Two isoforms of Xenopus retinoic acid receptor gamma 2 (B) exhibit differential expression and sensitivity to retinoic acid during embryogenesis.

We report the isolation of two retinoic acid receptor isoforms (RAR gamma), which differ only in the 5'untranslated and putative N-terminus A regions. The two isoforms appear to serve as early markers for the presumptive neural axis; however, their expression patterns differ. RAR-gamma 2.1 is first expressed at gastrulation at the dorsal lip and subsequently along the presumptive neural axis. RAR- gamma 2.2 represents the full-length sequence of a receptor cDNA already partially characterized and present as a maternal transcript [Ellinger-Ziegelbauer and Dreyer (1991); Genes Dev 5:94-104, (1993): Mech Dev 41:31-46; Pfeffer and DeRobertis, (1994) Mech Dev: 45:147-153]. Unlike RAR-gamma 2.2, the 2.1 variant is not expressed either in pre-somitic mesoderm or notochord. RAR-gamma 2.1 is strongly expressed in branchial arches and to a lesser extent in the neural floor plate. The two isoforms also exhibit differential sensitivity to retinoic acid. Constitutive expression of RAR gamma 2.2 following neurulation appears to be depressed by treatment with retinoic acid, but domains of highest expression, namely, the head and tail, remain relatively unaffected, as do patterns of expression prior to late neurulation. By contrast, RAR-gamma 2.1 is not transcribed in retinoid-inhibited structures. Using microinjection techniques, we show that changes of RAR-gamma 2.1 expression in presumptive head structures occur as an early and local consequence of retinoic acid administration. Since RAR-gamma 2.1 expression is inhibited by retinoic acid, we tested to see if other treatments that perturb axis formation had any effect. Surprisingly, UV irradiation did not suppress that its inhibition by retinoic acid is not due solely to inhibition of anterior neural development. These experiments demonstrate a new subdivision of isoforms that undergo differential expression during development and that exhibit differential sensitivity to retinoic acid and to UV. This sensitivity and the presence of this isoform variant in regions that are known to exhibit polarizing activity strengthen the hypothesis that these receptors play a primary role during morphogenesis.

Amino Acid Sequence↗

Factors influencing the success of sperm-cervical mucus interaction in patients exhibiting unexplained infertility.

The factors regulating the success of sperm-cervical mucus interaction in 46 patients exhibiting unexplained infertility were analyzed. Within this group of patients, considerable variation in the degree of mucus penetration, which appeared to be related to the properties exhibited by the spermatozoa rather than the quality of the mucus itself, was observed. The ability of the spermatozoa to fuse with zona-free hamster oocytes reflected their capacity for mucus penetration, regardless of whether human or bovine cervical mucus was used as the target. Multiple regression analysis also indicated the importance of the movement characteristics exhibited by the spermatozoa, which alone could account for up to 85% of the variability in mucus penetration. The concentration of motile spermatozoa and their linear velocity of progression influenced the number of spermatozoa penetrating the mucus in unit time, presumably through an effect on the frequency of collisions at the cervical mucus interface. Whether these collisions resulted in mucus penetration depended upon the movement characteristics of the spermatozoa and was positively associated with a "rolling" mode of progression and the amplitude of lateral sperm head displacement.

Animals↗

Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-beta 1.

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the positive regulation of angiogenesis in vivo, whereas it inhibits the proliferation of endothelial cells in vitro. To reconcile these apparently contradictory effects, we have investigated the effect of TGF-beta 1 on bovine aortic endothelial cells that exhibit spontaneous angiogenesis in vitro. We show that concentrations of TGF-beta 1 which stimulate proliferation of cells that form endothelial cords and/or tubes inhibit proliferation of the same cells grown at subconfluent densities. An increase in cell number of 35% over control cultures was achieved with 0.5 ng TGF-beta 1/ml. The proliferative effect was blocked by antibodies against TGF-beta. Immunological detection of BrdU-labeled nuclei revealed an increase greater than 220% in cells treated with TGF-beta 1. Moreover, a population of cells within the cords appeared to be a selective target for this cytokine. The stimulatory effect was not restricted to bovine aortic endothelial cells, as similar results were obtained with endothelial cells derived from rat microvessels. Significant levels of active TGF-beta 1 were detected in cultures containing cords/tubes, whereas only latent TGF-beta 1 was detected in subconfluent cultures. We show further that endothelial cells exhibiting angiogenesis in vitro secrete plasminogen activator, an enzyme that regulates activation of TGF-beta. The major increases in mRNA transcripts for extracellular matrix proteins that are typically associated with TGF-beta 1 were not seen in cells exhibiting angiogenesis in vitro. Since the formation of tubular networks requires both invasion and proliferation, we propose that TGF-beta 1 is a major morphoregulatory factor in angiogenesis that specifically controls endothelial cell proliferation and extracellular matrix turnover.

Animals↗

Establishment of human gastric epithelial (HGE) cell lines exhibiting barrier function, progenitor, and prezymogenic characteristics.

The unavailability of human cell lines representative of the gastric glandular epithelium while able to form a functional barrier restricts the application of a cell culture approach to the field of gastric epithelial physiology. In the current study, we have characterized new non-transfected clones isolated from gastric carcinoma cell lines known to express functional markers of the human gastric mucosa (J Cell Biochem 2001;81:241). Twenty-one clones exhibiting epithelial-type junctions (renamed HGE cell lines) were isolated from NCI-N87 (ATCC CRL 5822), whereas only squamous cell lines could be generated from other native strains. Of these 21 clones, HGE-17 and HGE-20 formed dense coherent monolayers and displayed true epithelial phenotype. E-cadherin and ZO-1 proteins were consistently localized at the periphery of all cells which also generated transepithelial electrical resistance. Moreover, growth factors known to be trophic for the gastric mucosa were able to stimulate mitogenesis at subconfluence. HGE-17 exhibited a poorly differentiated precursor-like status and responded strongly to EGF/TGFalpha treatment in restitution assays. HGE-20 cells, on the other hand, exhibited a higher degree of differentiation at the ultrastructural level as well as higher gastric lipase and pepsinogen levels. These latter zymogens were compartmentalized into granules which also contained mucin-6 (MUC6, prezymogenic-like status). Exogenous hormones, i.e., 1 mug/ml hydrocortisone and 5 microM retinoic acid, significantly increased enzyme levels in HGE-20. In conclusion, HGE-17 and HGE-20 represent the first human gastric cell lines with true epithelial characteristics, opening a venue to important applications for the study of re-epithelization, permeability, and regulation of digestive functions in the context of gastric physiology and pathology.

Artificial Organs↗

Members of the raf gene family exhibit segment-specific patterns of expression in mouse epididymis.

The proto-oncogene c-raf-1 and the related genes A-raf and B-raf encode serine/threonine protein kinases thought to be involved in regulating gene expression by acting as part of second-messenger signaling pathways within the cell. Among the tissues in which A-raf and c-raf-1 have been shown to be expressed was mouse epididymis. The present studies were undertaken to determine if the raf family genes exhibited specificity in their pattern of expression that might be indicative of specific function in the epididymis. Northern and in situ hybridization analyses demonstrated that c-raf-1 mRNA was expressed as a 3.1 kb transcript at uniform levels throughout the length of the epididymis in all types of epididymal epithelial cells. Neither the germ cell-specific testicular transcripts nor the somatic transcripts of B-raf were detected by either Northern or in situ hybridization analysis in any region of the epididymis. A-raf, expressed as two transcripts of 2.6 and 4.3 kb, was the only gene examined which exhibited a segment-specific pattern of expression, being highest in the principal epithelial cells of the proximal caput epididymis and decreasing progressively in more distal regions of the tubule. These studies indicate that each raf gene exhibits a characteristic pattern of expression in the epididymis; A-raf in particular may play a unique regulatory role in the regionalized functions of the epididymis.

Animals↗

Position 4 analogues of [deamino-Cys(1)] arginine vasopressin exhibit striking species differences for human and rat V(2)/V(1b) receptor selectivity.

Arginine vasopressin (AVP) mediates a wide variety of biological actions by acting on three distinct G-protein coupled receptors, termed V(1a) (vascular), V(1b) (pituitary) and V(2) (renal). It also binds to the oxytocin (OT) receptor. As part of a program aimed at the design of selective agonists for the human V(1b) receptor, we recently reported the human V(1b), V(1a), V(2) and OT receptor affinities of the following position 4 substituted analogues of [deamino-Cys(1)] arginine vasopressin (dAVP)-(1) d[Leu(4)]AVP, (2) d[Orn(4)]AVP, (3) d[Lys(4)]AVP, (4) d[Har(4)]AVP, (5) d[Arg(4)]AVP, (6) d[Val(4)]AVP, (7) d[Ala(4)]AVP, (8) d[Abu(4)]AVP, (9) d[Nva(4)]AVP, (10) d[Nle(4)]AVP, (11) d[Ile(4)]AVP, (12) d[Phe(4)]AVP, (13) d[Asn(4)]AVP, (14) d[Thr(4)]AVP: (15) d[Dap(4)]AVP. With the exception of Nos. 7 and 12, all peptides exhibit very high affinities for the human V(1b) receptor. Furthermore, peptides 1-4 exhibit high selectivities for the human V(1b) receptor with respect to the V(1a), V(2) and OT receptors and, with d[Cha(4)]AVP, in functional tests, are the first high affinity selective agonists for the human V(1b) receptor (Cheng LL et al., J. Med. Chem. 47: 2375-2388, 2004). We report here the pharmacological properties of peptides 1-4, 5 (from a resynthesis), 7, 9-13, 15 in rat bioassays (antidiuretic, vasopressor and oxytocic) (in vitro: no Mg(++)) with those previously reported for peptides 5, 6, 8, 14. We also report the rat V(1b), V(1a), V(2) and OT receptor affinities of peptides 1-5 and the rat V(2) receptor affinities for peptides: 7-15.The antidiuretic activities in units/mg of peptides 1-15, are: 1=378; 2=260; 3=35; 4=505; 5=748; 6=1150; 7=841; 8=1020; 9=877; 10=1141; 11=819, 12=110; 13=996; 14=758; 15=1053. Peptides 1-4 exhibit respectively the following rat and human (in brackets) V(2) receptor affinities: 1=3.1 nm (245 nm); 2=3.4 nm (1125 nm); 3=24.6 nm (11,170 nm); 4=0.6 nm (1386 nm). Their rat V(1b) receptor affinities are 1=0.02 nm; 2=0.45 nm; 3=9.8 nm; 4=0.32 nm. Their rat V(1a) receptor affinities are 1=1252 nm; 2=900 nm; 3=1478 nm; 4=32 nm. Their rat oxytocin (OT) receptor affinities are 1=481 nm; 2=997 nm; 3=5042 nm; 4=2996 nm. All four peptides have high affinities and selectivities for the rat V(1b) receptor with respect to the rat V(1a) and OT receptors. However, in contrast to their high selectivity for the human V(1b) receptor with respect to the human V(2) receptor, they are not selective for the V(1b) receptor with respect to the V(2) receptor in the rat. These findings confirm previous observations of profound species differences between the rat and human V(2) receptors. Peptides 1-4 are promising leads to the design of the first high affinity selective agonists for the rat V(1b) receptor.

Animals↗

Engineered porcine pepsinogen exhibits dominant unimolecular activation.

An engineered pepsinogen, which was a fusion protein of thioredoxin and pepsinogen, exhibited dominant self-activation (unimolecular reaction; intramolecular activation) in contrast to recombinant pepsinogen which exhibited both unimolecular and bimolecular reactions (intermolecular activation mediated by pepsin released during activation). At pH values of 1.1, 2.0, and 3.0, activation curves for the engineered pepsinogen were hyperbolic rather than sigmoidal, indicating that self-activation was the dominant activation mechanism in comparison to the slower bimolecular activation. To confirm which activation mechanism was dominant, an equal mole of pepsin was added to accelerate the bimolecular reaction during activation. The addition of exogenous pepsin did not affect the activation rate of the engineered pepsinogen but accelerated pepsinogen activation through the bimolecular reaction. The above results indicated that the engineered pepsinogen exhibited, primarily, a self-activation mechanism and that bimolecular activation was negligible.

Animals↗