Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions.

Aberrant expression of transforming growth factor beta 1 (TGF-beta 1) has been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions. To determine the in vivo effects of overexpression of TGF-beta 1 on the function and structure of hepatic as well as extrahepatic tissues, transgenic mice were generated containing a fusion gene (Alb/TGF-beta 1) consisting of modified porcine TGF-beta 1 cDNA under the control of the regulatory elements of the mouse albumin gene. Five transgenic lines were developed, all of which expressed the Alb/TGF-beta 1 transgene selectively in hepatocytes. The transgenic line 25 expressing the highest level of the transgene in the liver also had high (> 10-fold over control) plasma levels of TGF-beta 1. Hepatic fibrosis and apoptotic death of hepatocytes developed in all the transgenic lines but was more pronounced in line 25. The fibrotic process was characterized by deposition of collagen around individual hepatocytes and within the space of Disse in a radiating linear pattern. Several extrahepatic lesions developed in line 25, including glomerulonephritis and renal failure, arteritis and myocarditis, as well as atrophic changes in pancreas and testis. The results from this transgenic model strongly support the proposed etiological role for TGF-beta 1 in a variety of fibrotic and inflammatory disorders. The transgenic model may also provide an appropriate paradigm for testing therapeutic interventions aimed at neutralizing the detrimental effects of this important cytokine.

Characterization of histopathological lesions in a biological model for environmental studies: Eisenia andrei Bouché. Preliminar results

Introduction The strong expansion of the world production of plastics caused a severe accumulation of plastic debris in the environment, which makes them one of the most important contaminants, growing as a global environmental problem. Although the production in Europe has been relatively constant in the last 10 years, world plastic production continues to increase, affecting soil biota and their functions. Objectives Thus, in order to evaluate the effects of MP in soil-dwelling organisms, earthworms (Eisenia andrei Bouché), were exposed to standard artificial soil mixed with MPs and the authors documented, using microscopic figures, the pathological lesions found in this biological model. Material and Methods Eight adult earthworms extracted from soils contaminated with different concentrations of MP (mg/kgdw) with sizes ranging between 250-1000 m, were fixed in 10% neutral-buffered formalin and processed for routine histopathological diagnosis. Results and discussion Contrary to what would be expected, MP were not found throughout the GI tube of earthworms but several lesions were found in the individuals extracted from the soils with high MP concentrations, when compared with control group, namely epithelial intestinal atrophy and evidences of inflammatory responses to this stress agent. Conclusion Earthworms have probably avoided the consumption of the biggest MPs. However, evidences point for lesions that were likely caused by the smallest MPs that were likely egested during the depuration phase.

Masking odour when regrouping rabbit does: Effect on aggression, stress and lesions.

Regrouping female rabbits (Oryctolagus cuniculus) in group housing systems is a common management practice in Swiss rabbit breeding which may, however, induce agonistic interactions resulting in social stress and severe lesions. On farms using artificial insemination, does are usually kept singly for 12 days after parturition to avoid pseudopregnancy and fighting for nests. The integration of new group members usually occurs after this isolation phase. This study was conducted with 128 gravid does of the Hycole hybrid, housed in pens covering a floor area of 5.7 m2 that was bedded with straw and furnished with elevated areas, hiding places and eight compartments with nest boxes. In the experiment, the fur of 16 groups of 8 does each was sprayed with either alcohol or vinegar to mask the pre-existing group odours, or with water (control groups) shortly before regrouping. Lesion scores, stress parameters (body temperature and blood glucose level) and behaviour were assessed before and after the isolation phase. Effects of treatment and time on all collected parameters were analysed using mixed models. On the second day after regrouping 43% of the does showed new lesions. In the first five days after regrouping, new lesions occurred in 60% of the does; 32% had severe lesions. After regrouping, more agonistic interactions were observed and body temperature and blood glucose levels were higher than before regrouping (P<0.001 each). Body temperature increased less in groups treated with vinegar compared to the other two treatments on the first day after regrouping (P=0.017). In all other parameters no influence of the treatment with alcohol or vinegar was found. These findings suggest that masking the group odours with alcohol or vinegar had little effect on lesions, stress and agonistic interactions. Therefore, alternative management procedures need to be developed to reduce lesions and stress caused by aggressive behaviour.

Des lesions traumatiques que le foetus peut éprouver pendant l'accouchement : thèse presentée et soutenue publiquement par Ch. Pajot.

Memoria presentada al concurso para la Cátedra en la Universidad de París, Facultad de Medicina.

Lesions of the lower bowel.

Includes bibliography.

Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients

Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas,. including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16. (C) 2004 Elsevier Inc. All rights reserved.

Higher-level language deficits resulting from left primary cerebellar lesions

Background: Contemporary neuropsychological studies suggest that cerebellar lesions may impact upon higher-level cognitive functioning via mechanisms of crossed cerebello-cerebral diaschisis. Accordingly, right cerebellar lesions have been previously associated with linguistic impairments such as reduced word fluency and agrammatic output. Recently, however, neuroimaging investigations have also identified ipsilateral cerebral hypoperfusion as a consequence of cerebellar lesions, implicating a potential role for the left cerebellum in the mediation of language processes. Aims: The purpose of this research was to investigate the effects of left cerebellar lesions of vascular origin, on general as well as high-level language skills. Methods & Procedures: Linguistic profiles were compiled for five individuals with left primary cerebellar lesions utilising a comprehensive language test battery. Individual scores relevant to each subtest were compared to a group of non-neurologically impaired controls. The criterion for anomalous performance was established as greater than or equal to 1.5 SD below the mean of the control group. Outcomes & Results: The findings of this research suggest that higher-level language deficits may result from left primary cerebellar lesions. All participants demonstrated deficits on measures of word fluency, sentence construction within a set context, producing word definitions, and producing multiple definitions for the same word. Deficits were also noted for several participants on measures of understanding figurative language, forming word associations, identifying and correcting semantic absurdities, and producing synonyms and antonyms. Conclusions: The results presented challenge the notion of a lateralised linguistic cerebellum, supporting a potential role for the left as well as right cerebellar hemispheres in the regulation of language processes, presumably via cerebellar-basal ganglia/thalamo-cortical pathways.

Immunohistological analysis of Tannerella forsythia-induced lesions in a murine model

Tannerella forsythia has been implicated as a defined periodontal pathogen. In the present study a mouse model was used to determine the phenotype of leukocytes in the lesions induced by subcutaneous injections of either live (group A) or nonviable (group B) T. forsythia. Control mice (group C) received the vehicle only. Lesions were excised at days 1, 2, 4, and 7. An avidin-biotin immunoperoxidase method was used to stain infiltrating CD4(+) and CD8(+) T cells, CD14(+) macrophages, CD19(+) B cells, and neutrophils. Hematoxylin and eosin sections demonstrated lesions with central necrotic cores surrounded by neutrophils, macrophages and lymphocytes in both group A and group B mice. Lesions from control mice exhibited no or only occasional solitary leukocytes. In both groups A and B, neutrophils were the dominant leukocyte in the lesion 1 day after injection, the numbers decreasing over the 7-day experimental period. There was a relatively low mean percent of CD4(+) and CD8(+) T cells in the lesions and, whereas the percent of CD8(+) T cells remained constant, there was a significant increase in the percent of CD4(+) T cells at day 7. This increase was more evident in group A mice. The mean percent of CD14(+) macrophages and CD19(+) B cells remained low over the experimental period, although there was a significantly higher mean percent of CD19(+) B cells at day 1. In conclusion, the results showed that immunization of mice with live T. forsythia induced a stronger immune response than nonviable organisms. The inflammatory response presented as a nonspecific immune response with evidence of an adaptive (T-cell) response by day 7. Unlike Porphyromonas gingivalis, there was no inhibition of neutrophil migration.

Cervical Cancer Control, Priorities and New Directions

Cervical cancer is caused by infection with a range of high risk oncogenic human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc.

Factors influencing the number needed to excise: excision rates of pigmented lesions by general practitioners

Objective: To identify doctor and patient characteristics associated with excision of benign versus malignant pigmented skin lesions. Design, setting and participants: Retrospective audit of data on 4741 pigmented skin lesions excised from November 1998 to February 2000 by 468 general practitioners (39% response rate) from 223 practices in Perth, WA. (The data used were from the baseline period of a randomised controlled trial of a diagnostic aid for pigmented skin lesions.) Main outcome measure: The number needed to treat (NNT), defined as the number of pigmented lesions needed to be excised to identify one melanoma, in relation to demographic characteristics of GPs and patients. Results: Relatively more benign lesions were excised per melanoma (NNT = 83) in the youngest patients (aged 10-19 years) compared with the oldest (aged greater than or equal to 70) (NNT = 11) (P [trend]

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.

Disseminated Scedosporium prolificans infection and survival of a child with acute lymphoblastic leukemia

Scedosporium prolificans is a saprophytic fungus responsible for an increasing number of infections among immumocompromised hosts. Historically, disseminated infection with this organism has resulted in death. We report on a pediatric patient who developed overwhelming S. prolificans sepsis after induction chemotherapy for acute lymphoblastic leukemia. She is well 18 months after the diagnosis of fungal sepsis and continues to receive chemotherapy for leukemia, which remains in remission.