ABSTRACT
Evidence presented within a courtroom should be clear so that the members of the jury can understand it. The presentation of distressing images, such as human remains, can have a negative effect on the jury since photographic images may evoke emotional responses. Therefore, it is important to understand how other visual mediums may improve comprehension, bias, or distress individuals. For this study, 91 individuals were randomly assigned one of three visual evidence formats in a mock courtroom exercise. These included photographs, 3D visualisations, or a 3D-printed model. The results show that the use of 3D imaging improves the juror's understanding of technical language used within a courtroom, which in turn better informs the juror's in their decision-making.
Subject(s)
Audiovisual Aids , Comprehension , Decision Making , Expert Testimony , Forensic Sciences , Adult , Criminal Law , Female , Humans , Imaging, Three-Dimensional , Male , Photography , Printing, Three-DimensionalABSTRACT
Genital bullous pemphigoid (GBP) is a rare localized subset of bullous pemphigoid (BP). BP is characterized by autoantibodies against hemidesmosomes, which are involved in the structural integrity of the epidermis, and this results in subepidermal blistering. Typically, GBP affects women and children. We report an adult male who presented with a scrotal rash and blisters that developed into erosions. Only two previous cases in men have been reported. Immunofluoresence and histopathology confirmed the diagnosis of BP. The patient responded to mycophenolate mofetil and doxycycline.
Subject(s)
Pemphigoid, Bullous/pathology , Scrotum/pathology , Aged , Fluorescent Antibody Technique , Humans , Male , Pemphigoid, Bullous/diagnosisSubject(s)
Circumcision, Male/methods , Genital Diseases, Male/pathology , Penis/pathology , Porokeratosis/pathology , Adult , Genital Diseases, Male/surgery , Humans , Keratinocytes/pathology , Keratinocytes/ultrastructure , Male , Penis/surgery , Porokeratosis/surgery , Pruritus/diagnosis , Pruritus/etiologyABSTRACT
We describe two patients who received haematopoietic stem cell marrow transplantation, and developed male genital lichen sclerosus (MGLSc), one of whom also had squamous carcinoma in situ (Bowen disease). MGLSc has previously been associated with graft-versus-host disease. Various aetiological factors for LSc have been proposed, including a role for chronic occluded epithelial exposure to urine. A number of factors imply that the risk of malignant transformation in this bone marrow transplant group is likely to be higher than the overall figure of 2-9% cited for MGLSc. It is vital, therefore, that clinicians involved in the care of those with haematological malignancies are adequately prepared to examine the genitals of their patients, and to recognize and refer any suspect penile lesions.
Subject(s)
Bone Marrow Transplantation/adverse effects , Graft vs Host Disease/pathology , Lichen Sclerosus et Atrophicus/etiology , Penile Neoplasms/etiology , Adult , Humans , Male , Young AdultABSTRACT
BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair. It is divided into eight complementation groups: XP-A to XP-G (classical XP) and XP variant (XP-V). Severe and prolonged sunburn reactions on minimal sun exposure have been considered a cardinal feature of classical XP. However, it has recently become clear that not all patients have abnormal sunburn reactions. OBJECTIVES: To examine sunburn reactions in a cohort of patients with XP and correlate this to the complementation group. METHODS: Sixty patients with XP attending the U.K. National XP Service from 2010 to 2012 were studied. Their history of burning after minimal sun exposure was assessed using a newly developed sunburn severity score. The age at which the first skin cancer was histologically diagnosed in each patient, and the presence of any neurological abnormality, was also recorded. RESULTS: Sunburn severity scores were abnormally high in patients with XP-A, XP-D, XP-F and XP-G compared with non-XP controls. There was no significant difference in sunburn score of patients with XP-C, XP-E and XP-V compared with controls (P > 0·05). Patients with XP-C, XP-E and XP-V were more likely to have skin cancer diagnosed at an earlier age than those with severe sunburn on minimal sun exposure. In addition, patients with XP with severe sunburn had an increased frequency of neurological abnormalities. CONCLUSIONS: Not all patients with XP have a history of severe and prolonged sunburn on minimal sun exposure. The normal sunburn response of patients with XP-C, XP-E and XP-V may relate to the preservation of transcription-coupled DNA repair in these groups. Those with a history of severe sunburn on minimal sun exposure developed their first skin cancer at an older age compared with patients with XP-C, XP-E and XP-V, but they had an increased frequency of neurological abnormalities. Physicians need to be aware that about half of all patients with XP will present without a history of abnormal sunburn.
Subject(s)
Sunburn/pathology , Xeroderma Pigmentosum/pathology , Adolescent , Adult , Age of Onset , Case-Control Studies , Female , Humans , Kaplan-Meier Estimate , Male , Melanoma/ethnology , Melanoma/mortality , Melanoma/pathology , Middle Aged , Nervous System Diseases/ethnology , Nervous System Diseases/mortality , Nervous System Diseases/pathology , Skin Neoplasms/ethnology , Skin Neoplasms/pathology , Sunburn/ethnology , Sunburn/mortality , Xeroderma Pigmentosum/ethnology , Xeroderma Pigmentosum/mortality , Young AdultABSTRACT
Cockayne syndrome is an autosomal recessive multisystem disorder characterized principally by neurological and sensory impairment, cachectic dwarfism, and photosensitivity. This rare disease is linked to mutations in the CSB/ERCC6 and CSA/ERCC8 genes encoding proteins involved in the transcription-coupled DNA repair pathway. The clinical spectrum of Cockayne syndrome encompasses a wide range of severity from severe prenatal forms to mild and late-onset presentations. We have reviewed the 45 published mutations in CSA and CSB to date and we report 43 new mutations in these genes together with the corresponding clinical data. Among the 84 reported kindreds, 52 (62%) have mutations in the CSB gene. Many types of mutations are scattered along the whole coding sequence of both genes, but clusters of missense mutations can be recognized and highlight the role of particular motifs in the proteins. Genotype-phenotype correlation hypotheses are considered with regard to these new molecular and clinical data. Additional cases of molecular prenatal diagnosis are reported and the strategy for prenatal testing is discussed. Two web-based locus-specific databases have been created to list all identified variants and to allow the inclusion of future reports (www.umd.be/CSA/ and www.umd.be/CSB/).
Subject(s)
Cockayne Syndrome/genetics , DNA Helicases/genetics , DNA Repair Enzymes/genetics , Mutation/genetics , Transcription Factors/genetics , Amino Acid Sequence , Cockayne Syndrome/diagnosis , DNA Helicases/chemistry , DNA Repair Enzymes/chemistry , Databases, Genetic , Genetic Association Studies , Humans , Molecular Sequence Data , Poly-ADP-Ribose Binding Proteins , Polymorphism, Genetic , Sequence Alignment , Structure-Activity Relationship , Transcription Factors/chemistryABSTRACT
BACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive disorder of, in most cases, defective nucleotide excision repair (NER) of ultraviolet radiation (UV)- and chemical-induced DNA damage. The condition is characterized by an increased sensitivity of the skin to UV radiation, with early development of pigmentary changes and premalignant lesions in sun-exposed areas of the skin, signs of photoageing and a greatly increased incidence from a young age of skin tumours including melanoma. Approximately 20% of patients with XP show neurological abnormalities of varying severity due to primary neuronal degeneration. Genetic analysis by somatic cell hybridization has led to the identification in the NER-defective form of XP of seven complementation groups, designated XP-A to XP-G. These complementation groups correspond to different proteins involved in the NER process. XP-A classically includes some of the most severely affected patients. OBJECTIVES: We describe a 61-year-old Punjabi woman with XP. Remarkably she had only mild cutaneous abnormalities, minimal neurological features and unusual longevity, and developed a malignant spindle cell melanoma. There are few previous reports of spindle cell melanoma associated with XP. To gain insight into the aetiology of these unusual features, we sought to analyse the DNA repair properties of the patient and identify the complementation group and the causative mutation in the defective gene. METHODS: Unscheduled DNA synthesis and the inhibition of RNA synthesis were measured. The complementation group was assigned by fusing the cells of our patient with XP cells of known complementation groups and determining the ability to carry out unscheduled DNA repair. Molecular analysis of the cDNA was carried out by polymerase chain reaction and DNA sequencing. RESULTS: Levels of DNA repair were extremely low and complementation analysis assigned the defect to the XP-A group. Sequencing of the XPA gene revealed a novel homozygous mutation of A-->G at the eighth nucleotide of intron 4 causing aberrant splicing and a nonfunctional truncated XP-A protein. However, a small amount of normally spliced mRNA was detected at <5% the level in normal cells. CONCLUSIONS: The small amount of normally spliced mRNA detected may be sufficient to explain the relatively mild clinical features in our patient.
Subject(s)
Melanoma/genetics , Point Mutation , Skin Neoplasms/genetics , Xeroderma Pigmentosum Group A Protein/genetics , Afghanistan/ethnology , DNA Repair , Female , Genetic Complementation Test , Homozygote , Humans , London , Melanoma/complications , Melanoma/pathology , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Skin Neoplasms/complications , Skin Neoplasms/pathology , Xeroderma Pigmentosum/complications , Xeroderma Pigmentosum/genetics , Xeroderma Pigmentosum/pathologyABSTRACT
The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor TFIIH with DNA helicase activity. TFIIH has two functions, in basal transcription and nucleotide excision repair. Mutations in XPD that affect DNA repair but not transcription result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which there is no skin cancer predisposition, or in rare cases, XP combined with Cockayne syndrome. Up till now there have been no reports of combined clinical features of XP and TTD. We have now identified two patients with some features of both these disorders. One of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical developmental delay, has XPD mutations not previously reported, and barely detectable levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has been identified previously, but only in TTD patients with no features of XP. The level of repair of UV damage in XP38BR is substantially higher than that in other patients with the same mutation. With both patients, polarized light microscopy revealed a 'tiger-tail' appearance of the hair, and amino acid analysis of the hair shafts show levels of sulfur-containing proteins intermediate between those of normal and TTD individuals. Our findings highlight the complexities of genotype-phenotype relationships in the XPD gene.
Subject(s)
DNA Helicases , DNA-Binding Proteins , Hair Diseases/genetics , Proteins/genetics , Transcription Factors , Xeroderma Pigmentosum/genetics , Adult , Amino Acid Sequence , Apoptosis/radiation effects , Base Sequence , Cell Survival/radiation effects , Cells, Cultured , Child, Preschool , DNA Mutational Analysis , DNA, Complementary/chemistry , DNA, Complementary/genetics , Dose-Response Relationship, Radiation , Female , Hair Diseases/pathology , Humans , Mutation , Photosensitivity Disorders/genetics , Photosensitivity Disorders/pathology , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Ultraviolet Rays , Xeroderma Pigmentosum/pathology , Xeroderma Pigmentosum Group D ProteinABSTRACT
BACKGROUND AND AIMS: To determine whether the inclusion of 20 g free glutamine as part of the nitrogen source of parenteral feeds reduces length of hospital stay or mortality. METHODS: In a randomised, double blind, controlled trial in 168 patients clinically accepted for parenteral nutrition, standard feeds were compared with feeds in which 3.8 g of the total nitrogen was replaced with the equivalent 20 g glutamine. A minimum of 11 g nitrogen/day was used in all patients. Daily intakes of energy and nitrogen were determined using a validated computer protocol and were similar for the two groups. All feeds included trace elements, vitamins, electrolytes, and minerals. RESULTS: A total of 85 patients received a median of eight (interquartile range 5-13) daily feeds containing glutamine while 83 received a median of eight (5-15) standard feeds. No difference between groups was detected for infective complications. Twenty control patients and 14 who had received glutamine died during their hospital stay (NS). Median length of stay was 32 (23-52) days on glutamine, which was not significantly different from the control value of 35 (25-55) days. Glutamine was associated with a significant (p<0.03) reduction in length of stay in surgical patients (45 days (range 29-81) versus 30 days (range 19-54)). CONCLUSION: The benefit from glutamine supplementation of parenteral feeds as used in this trial has not been proved. Supplementation may have advantages in surgical patients and in haematological malignancy. Further trials are required.
Subject(s)
Glutamine/therapeutic use , Parenteral Nutrition/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cause of Death , Critical Care/methods , Double-Blind Method , Female , Glutamine/blood , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Postoperative Care/methods , Treatment OutcomeABSTRACT
The xeroderma pigmentosum group D (XPD) protein has a dual function, both in nucleotide excision repair of DNA damage and in basal transcription. Mutations in the XPD gene can result in three distinct clinical phenotypes, XP, trichothiodystrophy (TTD), and XP with Cockayne syndrome. To determine if the clinical phenotypes of XP and TTD can be attributed to the sites of the mutations, we have identified the mutations in a large group of TTD and XP-D patients. Most sites of mutations differed between XP and TTD, but there are three sites at which the same mutation is found in XP and TTD patients. Since the corresponding patients were all compound heterozygotes with different mutations in the two alleles, the alleles were tested separately in a yeast complementation assay. The mutations which are found in both XP and TTD patients behaved as null alleles, suggesting that the disease phenotype was determined by the other allele. If we eliminate the null mutations, the remaining mutagenic pattern is consistent with the site of the mutation determining the phenotype.
Subject(s)
DNA Helicases , DNA-Binding Proteins , Hair Diseases/genetics , Mutation , Proteins/genetics , Transcription Factors , Xeroderma Pigmentosum/genetics , Cell Line , DNA Repair/genetics , DNA Repair/radiation effects , Fibroblasts/radiation effects , Humans , Ultraviolet Rays , Xeroderma Pigmentosum Group D ProteinABSTRACT
The objective of this study was to determine whether poultry shell eggs are a major reservoir of Salmonella enteritidis in Arkansas. One hundred dozen commercially purchased shell eggs were cultured for the presence of Salmonella sp. After each dozen eggs was examined, the contents of the 12 eggs were separated from their shells. The contents and the shells were separately pooled and cultured. One dozen of the 100 dozen egg shells cultured were found to be externally contaminated with S heidelberg, while none of the contents of the 100 dozen eggs were found to contain Salmonella organisms. The reevaluation of previously obtained telephone follow-up data on 204 patients with Salmonella infections from 1992-1993 revealed that 30 had consumed raw eggs before their salmonellosis but only one patient was infected with S enteritidis. These data suggest that poultry shell eggs are not a major cause of human illness due to S enteritidis in Arkansas.
Subject(s)
Egg Shell/microbiology , Eggs/microbiology , Poultry/microbiology , Salmonella enteritidis/isolation & purification , Animals , Arkansas , Disease Reservoirs , Egg White/microbiology , Egg Yolk/microbiology , Follow-Up Studies , Food Microbiology , Humans , Prevalence , Salmonella/classification , Salmonella/isolation & purification , Salmonella Infections , TelephoneABSTRACT
Cockayne syndrome (CS) is an autosomal recessive disorder with dwarfism, mental retardation, sun sensitivity and a variety of other features. Cultured CS cells are hypersensitive to ultraviolet (UV) light, and following UV irradiation, CS cells are unable to restore RNA synthesis rates to normal levels. This has been attributed to a specific deficiency in CS cells in the ability to repair damage in actively transcribed regions of DNA at the rapid rate seen in normal cells. We have used the failure of recovery of RNA synthesis, following UV irradiation of CS cells, in a complementation test. Cells of different CS donors are fused. Restoration of normal RNA synthesis rates in UV-irradiated heterodikaryons indicates that the donors are in different complementation groups, whereas a failure to effect this recovery implies that they are in the same group. In an analysis of cell strains from 22 CS donors from several countries and different racial groups, we have assigned five cell strains to the CS-A group and the remaining 17 to CS-B. No obvious racial, clinical or cellular distinctions could be made between individuals in the two groups. Our analysis will assist the identification of mutations in the recently cloned CSA and CSB genes and the study of structure-function relationships.
Subject(s)
Cockayne Syndrome/genetics , Adult , Cells, Cultured , Child , Child, Preschool , Genetic Complementation Test , Humans , InfantSubject(s)
Nutritional Support/nursing , Adult , Female , Humans , Infection Control , Male , Middle Aged , Nutrition Assessment , Nutritional Requirements , Nutritional Support/methodsSubject(s)
Glucose/metabolism , Monosaccharide Transport Proteins/metabolism , Animals , Apoptosis , Biological Transport, Active , Cell Line , Female , Glucose Transporter Type 1 , Hematopoietic System/metabolism , Humans , Interleukin-3/pharmacology , Kinetics , Mammary Glands, Animal/metabolism , Oncogene Proteins v-abl/metabolism , Pregnancy , Protein-Tyrosine Kinases/metabolism , RatsABSTRACT
BACKGROUND: Myeloma is a plasma cell malignancy that usually presents with systemic manifestations or symptoms related to bone involvement. We describe the first case of crystalline protein deposition in the skin as the initial manifestation of myeloma. OBSERVATIONS: Crystals were found mainly in the extracellular space in the dermis of both involved and uninvolved skin in the absence of plasma cell infiltration. Crystals were also found in conjunctival tissue and bone marrow. CONCLUSIONS: We have described a unique case of myeloma that presented as facial and eyelid swelling. There were crystalline deposits in the skin and conjunctivae, but mechanisms of crystal formation and the factors causing local deposition were not established. However, treatment of the underlying disorder leads to resolution of the cutaneous features of crystal deposition.
Subject(s)
Multiple Myeloma/pathology , Skin Neoplasms/pathology , Biopsy , Crystallization , Humans , Male , Middle AgedABSTRACT
The sequential epitopes on bovine growth hormone (bGH) recognised by five polyclonal mouse antisera have been identified by scanning with multiple pin-bound peptides. Four main epitopes were identified at residues 29-40, 101-110, 139-152 and 181-191. Of these, only epitope 139-152 is recognised by all five mouse antisera indicating that, for the mouse, this may represent an immuno-dominant region of the bGH molecule.
Subject(s)
Growth Hormone/immunology , Immunodominant Epitopes/immunology , Amino Acid Sequence , Animals , Cattle , Enzyme-Linked Immunosorbent Assay , Female , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Peptide Fragments/immunology , Recombinant Proteins/immunologyABSTRACT
The decision of whether to withdraw or withhold nutritional support in terminally ill patients presents a multifaceted ethical dilemma. Any decision must, of course, be in the patient's best interests and in accordance with an interpretation of his or her wishes, but how can this be proved to be so?
Subject(s)
Decision Making, Organizational , Enteral Nutrition , Ethics, Nursing , Terminal Care , Withholding Treatment , Humans , Personal Autonomy , Quality of Life , Risk AssessmentABSTRACT
A recently developed technology called epitope scanning permits the rapid and accurate delineation of continuous stretches of amino acids in a protein which constitute the sequential epitopes recognised by an antiserum raised to that protein. In the present report, we describe the use of this technique to identify the epitopes in the recombinant bovine growth-hormone (rbGH) molecule recognised by three polyclonal guinea-pig antisera and two polyclonal rabbit antisera. The results obtained show that, for guinea-pig antisera, 3 or 4, very-well-defined major continuous epitopes are present. As would be expected given the intrinsic genetic factors (major histocompatibility restriction, antigen processing and presentation) controlling the immune response in individual animals, subtle differences are evident in the precise location and relative reactivities of these epitopes in different guinea-pig antisera. Nevertheless, there is a large degree of overlap in these epitopes, such that immunodominant regions of the antigen can be clearly delineated. In a structural sense, these epitopes share a common motif in that they are sited in areas of the protein antigen with little secondary structure (loop/coil), although there is some contribution by neighbouring alpha-helices. For the two rabbit antisera, the response tends to be rather more heterogeneous, with recognition of more peptides and less clearly defined epitopes than was the case with the guinea-pig antiserum. Comparison of the four guinea-pig epitopes, identified by our experimental methods with computer predictions for this molecule (Jameson-Wolf antigenic index), indicate that two are strongly predicted, one is weakly predicted and one is not predicted. These observations, together with the displayed intraspecies and interspecies variation clearly indicate the limitations of these predictive methods. In conclusion, we have demonstrated that, despite the expected variation in the exact location of continuous epitopes defined by different anti-rbGH sera, there are large regions of overlap defining immunogenic core regions within the molecule. We believe that studies of this nature, together with further understanding of antigen processing and peptide presentation to immune cells, may have a role to play in the development of candidate peptide vaccines.