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Intercellular adhesion molecule 1 (ICAM-1) is a central cell adhesion molecule for retinal transendothelial migration of the leukocytes in non-infectious posterior uveitis. Inhibiting ICAM1 gene transcription reduces induction of ICAM-1 in inflamed retinal endothelium. Based on published literature implicating transcription factor ETS-1 as an activator of ICAM1 gene transcription, we investigated the effect of ETS-1 blockade on ICAM-1 levels in cytokine-stimulated human retinal endothelial cells. We first examined ICAM1 and ETS1 transcript expression in human retinal endothelial cells exposed to tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1β). ICAM1 and ETS1 transcripts were increased in parallel in primary human retinal endothelial cell isolates (n = 5) after a 4-hour stimulation with TNF-α or IL-1β (p ≤ 0.012 and ≤ 0.032, respectively). We then assessed the effect of ETS-1 blockade by small interfering (si)RNA on cellular ICAM1 transcript and membrane-bound ICAM-1 protein. ETS1 transcript was reduced by greater than 90% in cytokine-stimulated and non-stimulated human retinal endothelial cell monolayers following a 48-hour treatment with two ETS-1-targeted siRNA, in comparison to negative control non-targeted siRNA (p ≤ 0.0002). The ETS-1 blockade did not reduce ICAM1 transcript expression nor levels of membrane-bound ICAM-1 protein, rather it increased both for a majority of siRNA-treatment and cytokine-stimulation conditions (p ≤ 0.018 and ≤ 0.004, respectively). These unexpected findings indicate that ETS-1 blockade increases ICAM-1 transcript and protein levels in human retinal endothelial cells. Thus ETS-1-targeting would be expected to promote rather than inhibit retinal transendothelial migration of leukocytes in non-infectious posterior uveitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Ma, Appukuttan, Lower, Lumsden, Michael, Smith and Ashander.)

Background: The COVID-19 pandemic has affected medical education, constraining clinical exposure and posing unprecedented challenges for students and junior doctors. This research explores the potential of artificial intelligence (AI), specifically the ChatGPT-4 language model, to transform medical education and address the deficiencies in clinical exposure during the post-pandemic era., Research Questions/purpose: What is the potential of AI large language models in delivering safe and coherent medical advice to junior doctors for clinical orthopaedic scenarios?, Patients and Methods: A series of diverse orthopaedic questions was presented to ChatGPT-4, from general medicine to highly specialised fields. The questions were based on a variety of common orthopaedic presentations including neck of femur fracture, compartment syndrome, pulmonary embolism, and a motor vehicle accident. A validated questionnaire (Likert Scale) was implemented to evaluate the answers produced by ChatGPT-4., Results: Our results indicate that ChatGPT-4 exhibits exceptional proficiency in delivering accurate and coherent medical advice. Its intuitive interface, accessibility, and sophisticated algorithm render it an ideal supplementary tool for medical students and junior doctors. Despite certain limitations, such as its inability to fully address highly specialised areas, this study highlights the potential of AI and ChatGPT-4 to revolutionise medical education and fill the clinical exposure void generated by the pandemic. Future research should concentrate on the practical application of ChatGPT-4 in real-world medical environments and its integration with other emerging technologies to optimise its influence on the education and training of healthcare professionals., Conclusions: ChatGPT-4's integration into orthopaedic education and practice can mitigate pandemic-related experience gaps, promoting self-directed, personalised learning and decision-making support for interns and residents. Future advancements may address limitations to enhance healthcare professionals' learning and expertise., Level of Evidence: Level III evidence-observational study., Competing Interests: Conflict of InterestThe authors declare no conflict of interest., (© Crown 2023.)

Background: Plantar fasciitis is a recurrent cause of heel pain and is often treated by corticosteroid infections (CSI). The current study reviewed and analysed the role of CSI with platelet rich plasma (PRP), and CSI with extracorporeal shock wave therapy (EWST) for plantar fasciitis treatment., Methods: PubMed, Medline, Web of Science, Embase, Cochrane, and Google Scholar databases were searched for relevant studies. Preferred Reporting in Systematic Review & Meta-Analysis (PRISMA) guidelines were used to search relevant studies published from infinity to April 2021. The risk of bias was performed using Cochrane Collaboration's tool. GRADE assessment was used for quality of evidence. Data analysis was performed with the use of R software and P < 0.05 was considered statistically significant. CSI was compared with PRP and EWST., Results: Eighteen studies comprising 1180 patients were included in this meta-analysis. When compared to PRP, CSI with lignocaine/lidocaine had significantly higher mean difference on visual analogue scale (VAS) pain scores at 3 months (0.62 [0.13; 1.12], P = 0.01) and 6 months (MD = 1.49 [0.22; 2.76], P = 0.02). At 6 months, VAS scores were higher in the CSI group than the ESWT group (MD = 0.8 [0.38; 1.22], P = 0.1). At 6 months, a significant reduction in the American Orthopaedic Foot and Ankle Score (AOFAS) was observed in the CSI group compared to PRP (MD = - 11.53 [- 16.62; - 6.43], P < 0.0001)., Conclusion: Patients suffering from plantar fasciitis, PRP achieved better VAS scores compared to CSI at 3 and 6-month follow-up. In addition, ESWT had better VAS score outcomes at 6 months compared to CSI. Regarding AOFAS score, PRP was more efficacious than CSI at 6 months of follow-up. Only through the development of high-quality, large-scale longitudinal studies, will the findings and conclusions of this meta-analysis be strengthened and influence our clinical practice in the treatment of plantar fasciitis., Level of Clinical Evidence: II., Competing Interests: Conflict of Interest The authors have no conflicts of interest to disclose., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Complex regional pain syndrome type 1 (CRPS-I) is a complex complication that occurs after limb extremity surgeries. Controversy exists regarding the effectiveness of vitamin C in reducing that condition. Therefore, we conducted this systematic review and meta-analysis to assess the role of vitamin C on CRPS-I and functional outcomes after distal radius, wrist, foot, and ankle surgeries. We searched Medline (via PubMed), Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar for relevant studies comparing perioperative vitamin C versus placebo after distal radius, wrist, foot, and ankle surgeries from infinity to May 2021. Continuous data such as functional outcomes and pain scores were pooled as mean differences, while dichotomous variables such as the incidence of complex regional pain syndrome and complications were pooled as odds ratios, with 95% confidence interval, using R software (meta package, version 4.9-0) for Windows. Eight studies were included. The timeframe for vitamin C administration in each study ranged from 42 to 50 days postinjury and/or surgical fixation. The effect size showed that vitamin C was associated with a decreased rate of CRPS-1 than placebo (odds ratio 0.33, 95% confidence interval [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (odds ratio 1.90, 95% confidence interval [0.99, 3.65]), functional outcomes (mean difference 6.37, 95% confidence interval [-1.40, 14.15]), and pain scores (mean difference -0.14, 95% confidence interval [-1.07, 0.79]). Overall, vitamin C was associated with a decreased rate of CRPS-I than placebo, while no significant difference was found regarding complications, functional outcomes, and pain scores. These results hold true when stratifying fracture type (distal radius, ankle, and foot surgeries) and vitamin C dose (500 mg or 1 g)., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: High tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) are commonly performed procedures for the treatment of compartmental knee osteoarthritis; however, the optimal procedure remains controversial. We conducted this systematic review and meta-analysis to compare the functional outcomes and assess complications and revision rates between the two techniques., Methods: We searched electronic databases for relevant studies comparing HTO versus UKA for unicompartmental knee osteoarthritis. Continuous data as visual analogue scale (VAS), range of motion, and free walking speed were pooled as mean differences (MDs). Dichotomous data as functional knee outcomes, complications, and revision were pooled as odds ratios (ORs), with 95% confidence interval (CI), using R software for windows., Results: Twenty-five studies involving 8185 patients were included. Meta-analysis showed that HTO was associated with higher risk of complications (OR = 2.47, 95% CI [1.52, 4.04]), poorer functional results (excellent/good) (OR = 0.32, 95% CI [0.21, 0.49]), and greater range of motion (MD = 7.05, 95% CI [2.41, 11.68]) compared to UKA. No significant differences were found between the compared groups in terms of VAS (MD = 0.14, 95% CI [- 0.08, 0.36]), revision rates (OR = 1.30, 95% CI [0.65, 2.60]), and free walking speed (MD = - 0.05, 95% CI [- 0.11, 0.00])., Conclusion: This study showed that UKA achieved fewer complications, better functional outcomes, and less range of motion compared to HTO. No significant differences were detected between HTO and UKA in terms of VAS and revision rate. Treatment options should be personalized to each patient considering factors such as their age, activities of daily living, their body mass index, and severity of osteoarthritis., Level of Evidence: II., Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00620-9., Competing Interests: Conflict of InterestIshith Seth declares that he has no conflict of interest. Nimish Seth declares that he has no conflict of interest. Gabriella Bulloch declares that she has no conflict of interest. Damien Gibson declares that he has no conflict of interest. Anish Rastogi declares that he has no conflict of interest. Kirk Lower declares that he has no conflict of interest. Aaron Rodwell declares that he has no conflict of interest. Warwick Bruce declares that he has no conflict of interest., (© Indian Orthopaedics Association 2022.)

The clinical significance of low-frequency deletions of 17p13 [tumour protein p53 (TP53)] in patients with chronic lymphocytic leukaemia (CLL) is currently unclear. Low-frequency del17p clones (<25%) were identified in 15/95 patients in the Australasian Leukaemia and Lymphoma Group (ALLG)/CLL Australian Research Consortium (CLLARC) CLL5 trial. Patients with low del17p, without tumour protein p53 (TP53) mutation, had significantly longer progression-free survival and overall survival durations than patients with high del17p clones. In 11/15 cases with low-frequency del17p, subclones solely with del17p or del13q were also noted. These data suggest that low-frequency del17p does not necessarily confer a poor outcome in CLL and challenges the notion of del13q as a founding event in CLL., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

In this study, we report on 8 compound heterozygotes for mutations in the key erythroid transcription factor Krüppel-like factor 1 in patients who presented with severe, transfusion-dependent hemolytic anemia. In most cases, the red cells were hypochromic and microcytic, consistent with abnormalities in hemoglobin synthesis. In addition, in many cases, the red cells resembled those seen in patients with membrane defects or enzymopathies, known as chronic nonspherocytic hemolytic anemia (CNSHA). Analysis of RNA and protein in primary erythroid cells from these individuals provided evidence of abnormal globin synthesis, with persistent expression of fetal hemoglobin and, most remarkably, expression of large quantities of embryonic globins in postnatal life. The red cell membranes were abnormal, most notably expressing reduced amounts of CD44 and, consequently, manifesting the rare In(Lu) blood group. Finally, all tested patients showed abnormally low levels of the red cell enzyme pyruvate kinase, a known cause of CNSHA. These patients define a new type of severe, transfusion-dependent CNSHA caused by mutations in a trans-acting factor (Krüppel-like factor 1) and reveal an important pathway regulating embryonic globin gene expression in adult humans.

The 0 K onset of C(3)H(6) --> C(3)H(5)(+) + H(*) is measured by threshold photoelectron-photoion coincidence (TPEPICO) spectroscopy. From the onset (11.898 +/- 0.025 eV) the heat of formation of the allyl ion (CH(2)CHCH(2)(+)) is determined to be DeltaH degrees (f,0K) = 967.2; DeltaH degrees (f,298K) = 955.4 +/- 2.5 kJ mol(-1). The value is significantly more positive than prior determinations, and resolves a discrepancy between measurements of the allyl radical and allyl ion heats of formation and recent highly precise measurements of the allyl radical adiabatic ionization energy. The new allyl ion heat of formation leads to a new proton affinity for propadiene (allene) of 765.0 +/- 2.6 kJ mol(-1). An attempt is made to determine the CH(3)CCH(2)(+) heat of formation by measuring the 0 K onset of 2-ClC(3)H(5) --> C(3)H(5)(+) + Cl(*). However, C(3)H(5)(+) appears at too low an energy to be the higher energy CH(3)CCH(2)(+) structure. Rather, 2-ClC(3)H(5)(+) undergoes a concerted hydrogen transfer and Cl-loss via an intramolecular S(N)2 like mechanism to produce the allyl ion. The 0 K onset of 3-ClC(3)H(5) --> C(3)H(5)(+) + Cl(*) (11.108 +/- 0.010 eV) is measured to determine the 3-ClC(3)H(5) heat of formation (DeltaH degrees (f,0K) = 14.9; DeltaH degrees (f,298K) = 1.1 +/- 2.7 kJ mol(-1)). 3-ClC(3)H(5)(+) is suggested to readily isomerize to trans 1-ClC(3)H(5)(+) prior to dissociation.

Although much is known about globin gene activation in erythroid cells, relatively little is known about how these genes are silenced in nonerythroid tissues. Here we show that the human alpha- and beta-globin genes are silenced by fundamentally different mechanisms. The alpha-genes, which are surrounded by widely expressed genes in a gene dense region of the genome, are silenced very early in development via recruitment of the Polycomb (PcG) complex. By contrast, the beta-globin genes, which lie in a relatively gene-poor chromosomal region, are not bound by this complex in nonerythroid cells. The PcG complex seems to be recruited to the alpha-cluster by sequences within the CpG islands associated with their promoters; the beta-globin promoters do not lie within such islands. Chromatin associated with the alpha-globin cluster is modified by histone methylation (H3K27me3), and silencing in vivo is mediated by the localized activity of histone deacetylases (HDACs). The repressive (PcG/HDAC) machinery is removed as hematopoietic progenitors differentiate to form erythroid cells. The alpha- and beta-globin genes thus illustrate important, contrasting mechanisms by which cell-specific hematopoietic genes (and tissue-specific genes in general) may be silenced.

Background: Börjeson-Forssman-Lehmann syndrome (BFLS; MIM 301900) is an infrequently described X linked disorder caused by mutations in PHF6, a novel zinc finger gene of unknown function., Objective: To present the results of mutation screening in individuals referred for PHF6 testing and discuss the value of prior X-inactivation testing in the mothers of these individuals., Results: 25 unrelated individuals were screened (24 male, one female). Five PHF6 mutations were detected, two of which (c.940A-->G and c.27&#95;28insA) were novel. One of these new mutations, c.27&#95;28insA, was identified in a female BFLS patient. This was shown to be a de novo mutation arising on the paternal chromosome. This is the first report of a clinically diagnosed BFLS female with a confirmed PHF6 mutation. In addition, the X-inactivation status of the mothers of 19 males with suggested clinical diagnosis of BFLS was determined. Skewed (> or =70%) X-inactivation was present in five mothers, three of whom had sons in whom a PHF6 mutation was detected. The mutation positive female also showed skewing., Conclusions: The results indicate that the success of PHF6 screening in males suspected of having BFLS is markedly increased if there is a positive family history and/or skewed X-inactivation is found in the mother.

Over the past 50 years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the alpha- and beta-globin genes are normally regulated and documenting the effects of inherited mutations that cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans-acting mutations are being found more often. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression that, in turn, may open up new avenues for improving the management of patients with common types of thalassemia.

The usual description of the Börjeson-Forssman-Lehmann syndrome (BFLS) is that of a rare, X-linked, partially dominant condition with severe intellectual disability, epilepsy, microcephaly, coarse facial features, long ears, short stature, obesity, gynecomastia, tapering fingers, and shortened toes. Recently, mutations have been identified in the PHF6 gene in nine families with this syndrome. The clinical history and physical findings in the affected males reveal that the phenotype is milder and more variable than previously described and evolves with age. Generally, in the first year, the babies are floppy, with failure to thrive, big ears, and small external genitalia. As schoolboys, the picture is one of learning problems, moderate short stature, with emerging truncal obesity and gynecomastia. Head circumferences are usually normal, and macrocephaly may be seen. Big ears and small genitalia remain. The toes are short and fingers tapered and malleable. In late adolescence and adult life, the classically described heavy facial appearance emerges. Some heterozygous females show milder clinical features such as tapering fingers and shortened toes. Twenty percent have significant learning problems, and 95% have skewed X inactivation. We conclude that this syndrome may be underdiagnosed in males in their early years and missed altogether in isolated heterozygous females.

Background/aims: Two half-brothers with similar malformed genitals, who both inherited a maternally derived t(X;5)(q13;p15) translocation, have a phenotype consistent with partial androgen sensitivity syndrome. The aim was to identify the gene disrupted by the X chromosome breakpoint., Methods: The breakpoint was localized using fluorescence in situ hybridization to metaphase spreads of the translocation., Results: The breakpoint on the X chromosome of the X;5 translocation was localized to a 30-kb region. This region does not contain any identified genes or transcripts. However, the breakpoint is approximately 134 kb from the 5' end of the androgen receptor (AR) gene., Conclusions: Genetic defects of the AR gene are collectively called androgen insensitivity syndrome and include a range of phenotypes from normal males, often with associated sterility, to XY females. The phenotype seen in the males with the t(X;5) is consistent with this syndrome. The analysis of the chromosomal abnormality suggests that this translocation may remove one or more upstream regulatory elements of the AR gene that are essential for its normal expression and its role in typical external masculinization., (Copyright (c) 2004 S. Karger AG, Basel.)

We describe two brothers with Borjeson-Forssman-Lehmann syndrome and the 22A-->T (Lys8X) PHF6 mutation, who presented with the symptoms and signs of multiple pituitary hormone deficiency. Biochemical investigations and radiology confirmed growth hormone (GH), thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH) as well as gonadotrophin deficiency. They were also found to have optic nerve hypoplasia. This family suggests that the BFL gene product may play an important role in midline neuro-development including the hypothalamo-pituitary axis.

Objective: To determine whether topical application of a 10% fipronil solution would control signs of flea allergic dermatitis in cats housed under natural conditions., Design: Multicenter open clinical trial., Animals: 42 client-owned cats with flea allergic dermatitis., Procedures: Study cats along with all other cats and dogs living in the same houses were treated with 10% fipronil solution topically on days 0, 30, and 60. Flea counts and clinical assessments were performed on study cats on days 0, 14, 30, 60, and 90., Results: Percentage reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day-0 geometric mean count, were 75, 73, 85, and 94%, respectively. Pruritus score was significantly improved at each examination after day 0, and pruritus was reduced or eliminated in 31 of 40 (78%) cats at the final examination. Similarly, scores for severity of miliary dermatitis and alopecia were significantly improved at each examination, except for alopecia score on day 14. Overall treatment efficacy, assessed on day 90, was excellent for 28 (70%) cats, good for 6 (15%), moderate for 3 (7.5%), and poor for 3 (7.5%)., Conclusions and Clinical Relevance: Results suggest that monthly topical application of fipronil is effective for treatment of flea allergic dermatitis in cats housed under natural conditions.

Canine scabies is a challenging disease to diagnose because sarcoptic mites are hard to find on skin scrapings. The purpose of this study was to evaluate a serologic enzyme-linked immunosorbent assay (ELISA) as an aid in the diagnosis of canine scabies. In addition, serum samples were obtained post treatment to determine the duration and persistence of circulating scabies antibodies after resolution of natural infection. Nineteen dogs diagnosed with sarcoptic mange and 38 control dogs were tested. Sixteen scabies-infested dogs showed positive pretreatment ELISA results (84.2% sensitivity). Thirty-four control dogs showed negative ELISA results (89.5% specificity). In the 11 scabies dogs from which multiple post treatment serum samples were obtained, detectable antibodies were not present 1 month after treatment in four cases, but were present for 1-4.5 months post treatment in seven dogs. Our results suggest that this scabies ELISA test is useful in the diagnosis of canine scabies.

Mental retardation or intellectual disability is a heterogeneous group of disorders of the human brain affecting 2-3% of the general population. It is becoming evident that a large proportion of mental retardation is genetically determined, which means that it can be molecularly defined and thus precisely diagnosed. Building knowledge and understanding about molecular processes leading to 'malfunction of human brain' will clearly bring benefits to patient management, disease prevention and ultimately disease treatment and will also assist in tackling much harder questions of the molecular basis of human cognitive ability. In this review the current knowledge of the molecular genetics of X-chromosome-linked mental retardation and its nonspecific forms in particular is discussed, together with limitations affecting diagnosis and likely new approaches that need to be implemented.

Börjeson-Forssman-Lehmann syndrome (BFLS) is a syndromic X-linked mental retardation that has been mapped by linkage to Xq26-q27. A nonsyndromic mental retardation family, MRX27, has also been localized to a region of the X chromosome overlapping Xq26-q27. The gene for ARHGEF6 (also known as alphaPIX or Cool-2), a newly identified guanine nucleotide exchange factor, was identified as a potential candidate XLMR gene, due to its location within the BFLS and MRX27 critical regions and its function in the regulation of PAK3 (a known MRX gene). The full coding sequence and genomic structure of the gene for ARHGEF6 was established in silico, based on available genomic, EST, and cDNA sequence information. Mutation analysis in BFLS- and MRX27-affected individuals was carried out. No mutations were found in two BFLS families or MRX27. Although ARHGEF6 is unlikely to be the gene responsible for either BFLS or MRX27, it remains a prime candidate for nonspecific or syndromic mental retardation linked to Xq26., (Copyright 2001 Wiley-Liss, Inc.)

Bobcats (Lynx rufus) are the reservoir hosts for Cytauxzoon felis, the causative agent of cytauxzoonosis. Cytauxzoonosis is a highly fatal tickborne blood protozoal disease of domestic and exotic cats. Treatment of clinically affected cats has generally been unrewarding. In our report, 6 of 7 cats had signs of illness and laboratory findings indicative of cytauxzoonosis and were successfully treated with 2 i.m. injections of diminazene aceturate or imidocarb dipropionate (2 mg/kg [0.9 mg/lb] of body weight, each). One cat died after the first injection of diminazene. Additional treatment with isotonic fluids i.v. and heparin s.c. were used as supportive care for dehydration and disseminated intravascular coagulation that were detected by laboratory testing between diminazene or imidocarb treatments. Atropine was effective in recovery and preventing adverse reactions associated with imidocarb treatment of 1 cat.

Loss of heterozygosity involving the long arm of chromosome 16 is a frequent event seen in a number of human carcinomas, including breast, prostate, hepatocellular, and ovarian cancers. A region found to be commonly deleted in breast and prostate carcinomas is located at 16q24.3, which suggests the presence of a tumor suppressor gene that may be altered in these two malignancies. A detailed physical and transcription map of this region that includes the loci defining the smallest region of deletion has been constructed. This report describes the characterization of a transcript located in this region, the growth arrest-specific 11 (GAS11) gene, which was viewed as a potential tumor suppressor gene due to the expression of its mouse homolog specifically during growth arrest. The gene consists of 11 exons spanning approximately 25 kb. Northern blot analysis identified two ubiquitously expressed mRNAs of 3.4 and 1.8 kb produced by the use of alternative polyadenylation sites. Another gene, C16orf3 (chromosome 16 open reading frame 3), was found to lie within intron 2 of GAS11. This gene appears intronless, is transcribed in the orientation opposite to that of GAS11, and is expressed at low levels. These genes were examined for mutations in breast tumor DNA, and both were excluded as tumor suppressor genes involved in breast cancer., (Copyright 1998 Academic Press.)

A breast cancer tumor suppressor gene has been localized to chromosome 16q24.3 by loss of heterozygosity (LOH) studies of breast tumor DNA. To identify candidate genes for this suppressor function, we have constructed a detailed physical map extending approximately 940 kb from the telomere of the long arm of chromosome 16 that encompasses the minimum LOH interval. This contig consists of a minimum overlapping set of 35 cosmids and a single PAC clone that were aligned by restriction enzyme site mapping. Cosmids were initially identified by screening filters with markers localized to the region by physical mapping using mouse/human somatic cell hybrids, and subsequently cosmid ends were used to complete the contig. A total of seven known genes, including PRSM1, PISSLRE, and the recently cloned Fanconi anemia A (FAA) gene, and potential transcripts from exon-trapping experiments have been located to this contig. A minimum of 14 new transcripts have been identified based on homology of trapped exons with database sequences. This contig and expressed sequence map will form the basis for the identification of the breast cancer tumor suppressor gene in this region., (Copyright 1998 Academic Press.)

A case-control study of nasal cancer in pet dogs was conducted to test the hypothesis that exposure to environmental tobacco smoke increases risk. Cases (n = 103) were selected from a teaching hospital during 1986-1990. Controls (n = 378) with other forms of cancer were selected from the same study base. Exposure to environmental tobacco smoke was evaluated by determining the number of smokers in the household, the packs of cigarettes smoked per day at home by each smoker, the number of years that each person smoked during the dog's lifetime, and the proportion of time spent indoors by the dog. The crude odds ratio for exposure to environmental tobacco smoke was 1.1 (95% confidence interval (CI) 0.7-1.8) and was unchanged after adjustment for confounders. Skull shape was found to exert a pronounced modifying effect; among dolichocephalic (long-nosed) dogs, the odds ratio for a smoker in the house was 2.0 (95% CI 1.0-4.1). A monotonic increase in the odds ratios across strata of total packs smoked and total indoor exposure to environmental tobacco smoke was found in this group of dogs, with risks of approximately 2.5 for the highest stratum. Conversely, all odds ratios for exposure to environmental tobacco smoke among short- and medium-length-nosed dogs were approximately 0.5. The data support an association between environmental tobacco smoke and canine nasal cancer.

A hospital-based case-control study was conducted to determine whether residential exposure to magnetic fields increased risk for canine lymphoma in pet dogs. Cases were patients at a veterinary teaching hospital with histologically confirmed lymphoma diagnosed between 1987 and 1990. Hospital controls with other forms of cancer were obtained by frequency matching on zip code and year of diagnosis. Information regarding the dog's activity patterns, residence history, and exposure to potential confounders was obtained by telephone interview. Wire codes and magnetic fields were measured at the homes at diagnosis of 93 cases and 137 controls. When exposure was categorized into two levels (high or very high wire codes compared with low, very low, or buried lines), the risk was elevated (odds ratio (OR) = 1.6, 95% confidence interval (CI) 0.9-2.9) and increased (OR = 1.8, 95% CI 0.9-3.4) after adjustment for potential confounders. Dogs that lived in homes with very high current codes had the highest risk (OR = 6.8, 95% CI 1.6-28.5). Moderate, imprecise increases in risk (odds ratios of 1.5-1.9) were found for residence in a home with a sidewalk (plumbing), backyard, or front yard magnetic field of 2.0 mG or greater, but not for indoor measurements at this level. Risk increased among dogs that spent more than 25% of the day outdoors. Laboratory and observational studies of dogs as an animal model for the effects of magnetic fields are recommended.