X/Y shaped periorbital reconstructive surgery following enucleation or exenteration in dogs and cats: 24 cases (2013-2020).

OBJECTIVES: To describe the X/Y shaped periorbital reconstruction technique following enucleation or exenteration in dogs and cats and to evaluate its cosmetic and functional results. MATERIALS AND METHODS: Medical records of dogs and cats from two different institutions that required enucleation or exenteration, followed by an additional X or Y plasty using fibrous periorbital tissue for cosmetic reasons, were retrospectively reviewed. All patients were evaluated clinically at 1-2 weeks, 2 months and 6 months. The eyelid sinking was scored as absent or present. RESULTS: Nineteen dogs and five cats were included in the study. Twelve dogs and three cats had an enucleation, while the remaining seven dogs and two cats underwent exenteration. In the short-term follow up, three patients had periorbital oedema. Sixty days and 6 months post-surgery, two cats and two dogs showed eyelid depression. These two dogs were both dolichocephalic breeds. The rest of the patients showed no eyelid sinking, while the periorbital oedema observed in the short-term follow up in the two dogs and one cat had completely resolved. The four patients with ocular neoplasia did not have the 6 months follow up, because of fatal metastatic disease or euthanasia. CLINICAL SIGNIFICANCE: The X/Y periorbital reconstructive procedure is quick, easy to perform and it provided satisfying long-term cosmetic results, except for four cases that developed eyelid depression.

Diethylnitrosamine enhances hepatic tumorigenic pathways in mice fed with high fat diet (Hfd).

Obesity has been implicated in the genesis of metabolic syndromes including insulin resistance and Type 2 Diabetes Mellitus (T2DM). Given the association between T2DM and the risk of hepatocellular carcinoma (HCC), our specific goal was to determine whether the liver of HFD-induced T2DM mice is more sensitive to the carcinogen diethylnitrosamine (DEN), due to a modification of the molecular pathways implicated in the early stages of HCC pathogenesis. C57BL/6 male mice (five-week-old) were divided into 4 groups: C, C + DEN, HFD and HFD + DEN. Mice were euthanized twenty-five weeks after DEN-injection. Livers of HDF-fed mice showed a higher proliferative index than Control groups. In line with this, HFD groups showed an increase of nuclear ß-catenin, and interestingly, DEN treatment led to a slight increase in the expression of this protein in HFD group. Based on these results, and to confirm this effect, we analyzed ß-catenin target genes, finding that DEN treatment in HFD group led to a significant increase of Vegf, c-myc, c-jun and cyclin D1 expression levels. According to our results, the expression of TCF4 showed to be significantly increased in HFD + DEN vs. HFD. In this regard, the ß-catenin/TCF4 complex enhanced its association with pSmads 2/3, as we observed an increase of nuclear Smads expression in HFD + DEN, suggesting a possible role of TGF-ß1/Smads signaling pathway in this phenomenon. Our results show that the liver of HFD fed model that resembles early T2DM pathology in mice, is more sensitive to DEN, by inducing both Wnt/ß-catenin and TGF ß1/Smads tumorigenic pathways.

Aberrant right subclavian artery causing megaoesophagus in three cats.

Three entire, domestic, shorthair male cats (age range: 3 months to 5 years) were referred because of regurgitation. Megaoesophagus attributable to aberrant right subclavian artery, originating from the aorta at the level of the fourth intercostal space, was diagnosed in all cats using thoracic radiography and CT angiography. One cat had concurrent patent ductus arteriosus with a normal aortic arch. Three-dimensional volume-rendered CT images were used to assess the malformations and to plan surgery for the treatment of the vascular anomalies. Different surgical approaches were used in the two kittens. The third cat was not operated. CT angiography is well suited for preoperative planning in cats with aberrant right subclavian artery alone or in combination with other vascular anomalies.

Diethylnitrosamine Increases Proliferation in Early Stages of Hepatic Carcinogenesis in Insulin-Treated Type 1 Diabetic Mice.

Diethylnitrosamine (DEN) induces hepatocarcinogenesis, increasing mitotic hepatocytes and leading to chronic inflammation. In addition, type 1 diabetes mellitus (T1DM) is also characterized by a proinflammatory state and by requiring insulin exogenous treatment. Given the association of diabetes, insulin treatment, and cell proliferation, our specific goal was to determine whether the liver in the diabetic state presents a greater response to DEN-induced cell cycle alteration, which is essential for the malignant transformation. Male C57BL/6 mice (four-week-old) were divided into 4 groups: C, C + DEN, T1DM, and T1DM + DEN. Mice were euthanized ten weeks after DEN injection. DEN per se produced an increase in liver lipid peroxidation levels. Besides, in T1DM + DEN, we found a greater increase in the proliferation index, in comparison with C + DEN. These results are in agreement with the increased expression observed in cell cycle progression markers: cyclin D1 and E1. In addition, a proapoptotic factor, such as activated caspase-3, evidenced a decrease in T1DM + DEN, while the Vascular Endothelial Growth Factor (VEGF) and the protooncogene p53 showed a higher increase with respect to C + DEN. Overall, the results allow us to highlight a major DEN response in T1DM, which may explain in part the greater predisposition to the development of hepatocarcinoma (HCC) during the diabetic state.

"Coxa pedis" today.

UNLABELLED: Coxa pedis is the talocalcaneonavicular joint and is the distal enarthrosis of the lower limb. It is defined coxa because of: (1) the enarthrosic meaning from an anatomical point of view, (2) the analogy to the hip. The stabilising devices are structural, passive and active; the corresponding pathology is the "Coxa pedis destabilising syndrome". During walking, release and stiffening of the foot are related to the opening and closure of the kinetic chain of the coxa pedis: it is mutually reversible, while opening is a passive event, closure is an active one. Considering the importance of the flexor digitorum longus muscle in stabilising the coxa pedis, is it logical transferring it in the tibialis posterior disfunction? During walking, opening and closure of the kinetic chain of the coxa pedis intervene in the opening and closure of the kinetic chain of the entire lower limb. The kinetic chain closes starting from the bottom and moving upwards in the foot-knee-hip progression, and opens starting from the top and moving downwards. Even rotations along the orthogonal plane of the segmental axes of the limb contribute to the closure of the kinetic chain, coxa pedis dysmorphism (cavovalgus foot: false flat foot) can cause, during growth, dysmorphism of the hip (residual anteversion) and of the knee (condyles or tibial tuberosity) instead of the reverse. ISSUES: subtalar joint; anomalous subtalar pronation syndrome; flexor digitorum longum transfer pro tibialis posterior tendon; coxa pedis actor or participant in the functional integration of the lower limb; anterior knee pain syndrome.

External quality assessment programmes for detection of HCV RNA, HIV RNA and HBV DNA in plasma: improved proficiency of the participants observed over a 2-year period.

BACKGROUND AND OBJECTIVES: Two External Quality Assessment Programmes (EQAPs) were run in 2008 and 2009 to evaluate the proficiency of blood centres in detecting, by nucleic acid amplification techniques (NAT), the possible contamination of plasma with hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV). MATERIALS AND METHODS: In the EQAP-2008, three customized panels were designed; each containing positive samples with a viral nominal concentration for the three viruses of about three times the 95% DL of the respective commercial NAT assay. In the EQAP-2009, the proficiency of the participants was evaluated with a single panel, independently on the NAT method used. RESULTS: While 84% (102/122) of the participants in the EQAP-2008 correctly identified the positive and negative samples of the panels, in the EQAP-2009 the percentage of proficient laboratories increased to 97% (118/122). Most importantly, in this 2-year experience, we observed a decrease in the number of pre-/postanalytical errors, from 14 in 2008 to two in 2009. CONCLUSIONS: The design of these two EQAPs allowed participants to assess the performance of the NAT methods applied in their routine screening of blood donations, not only with respect to analytical errors but also to human errors that, despite the high level of automation reached by NAT methods, can still occur.

External quality assessment for the detection of HCV RNA, HIV RNA and HBV DNA in plasma by nucleic acid amplification technology: a novel approach.

BACKGROUND AND OBJECTIVES: In this EQA study a novel approach was used to assess the performance of blood centres and blood product manufacturers in detecting the possible contamination of plasma with HCV, HIV and HBV by NAT. MATERIALS AND METHODS: A panel of 12 samples, three negative and three positive for each virus, was distributed to the EQA participants. The positive samples were prepared, using the respective WHO standards, in order to obtain a viral concentration of about three times the 95% DL of the methods most commonly used by laboratories involved in blood screening by NAT. Participants were requested to test each sample of the panel on different days, possibly by different operators using their routine NAT assay. RESULTS: Overall, the participants' performance was satisfactory. In particular, 49 of the 59 participants (83%) were able to correctly identify all samples. Regarding the remaining 10 laboratories, in three cases a deviation from the laboratory's procedure that could be attributed to an operator's mistake was observed, in two cases a possible cross-contamination occurred while in the remaining five cases the failure to detect the positive samples couldn't be ascribed to any relevant deviation in the laboratory's procedure. CONCLUSIONS: The novel design of this EQA study allowed participants to verify their day by day activity as the study was carried out in the context of their routine testing. Under these conditions, it was demonstrated that, despite the high level of automation reached by NAT assays, human errors can still occur.

Effect of a hydrocolloid dressing on first intention healing surgical wounds in the dog: a pilot study.

OBJECTIVES: To evaluate the efficacy of a hydrocolloid dressing for the treatment of surgical wounds in dogs. METHODS: Six healthy young female dogs of medium size and different breed underwent ovariohysterectomy. Histological evaluation was performed on biopsies taken from the edges of the wounds at day 7. The dressing was applied on one half of the wound according to manufacturer's instructions; the second half served as control. Biopsy specimens were fixed in a 10% formalin buffered solution pH 7.4, paraffin embedded and stained with haematoxylin and eosin. For clinical assessment, the presence and quality of exudate, erythema of the surrounding area, swelling and correct apposition of the wound margins were evaluated. RESULTS: The hydrocolloid dressing was easy to use. The clinical quality of the treated skin wounds was superior to the non-treated ones. Comparison of histological features between treated and untreated wounds showed a more regular organisation of the granulation tissue in the treated wounds, with fibroblasts being aligned parallel to the overlying epidermis. The number of inflammatory cells and the extension of granulation tissue were less prominent and less widespread in treated compared to untreated wounds. CONCLUSION: The dressing performed very well in terms of adhesiveness and flexibility. It was useful in the management of surgical wounds to avoid contamination and ameliorate the epithelialisation rate and granulation tissue morphology of the surgical scar.

[Knowledge and use of Pap-smear among HIV-positive women]. / Importanza della conoscenza del Pap-test e suo utilizzo tra le donne HIV-positive.

AIM: HIV-positive women are at increased risk for preneoplastic lesions and invasive cervical cancer (ICC). The occurrence of these lesions can be substantially reduced by appropriate cervico-vaginal screening protocols (i.e., Pap-test). The aim of study was to assess: 1) awareness of Pap-smear and 2) the association between awareness of Pap-smear and screening attitudes of HIV-positive women. METHODS: Three-hundred and ninety HIV-positive women who attended the HIV outpatient gynecological unit of the National Institute for Infectious Diseases, Rome, from January 2003 to April 2005 were included in this investigation. These 390 women were interviewed to assess whether they were aware that Pap-test was a preventive tool against cervical cancer. In addition, past history of Pap-test, socioeconomic condition, history of HIV infection, and sexual habits were investigated. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the association between knowledge of Pap-test and covariates. RESULTS: Of these 390 HIV-positive women, 54.6% were not aware that Pap-test could prevent ICC. Women with a low educational level (OR = 6.6) or women who originated from Africa (OR = 6.5) were more likely to be unaware of Pap-test. Lack of Pap-test awareness was strongly associated with negative history for lifetime Pap-test (OR = 4.7). CONCLUSIONS: We showed that a large proportion of HIV-infected women are not aware that ICC could be prevented through Pap-test screening, and that lack of Pap-test screening is strongly associated with lack of awareness. The need for Pap-test counseling targeted to HIV-infected women clearly emerges from our findings.

The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: a preliminary study of autocrine and paracrine loops.

Vascular Endothelial Growth Factor (VEGF) and its receptor KDR are involved in the regulation of angiogenesis and are up-regulated in a number of tumours in humans and in particular, breast cancer. We therefore evaluated the prognostic potential of the angiogenetic process in feline and canine mammary carcinomas by the immunohistochemical assessment of VEGF expression and micro vessel density (MVD) quantification and examined the interplay between VEGF and KDR. These variables were related to some relevant clinicopathological parameters and to overall survival (OS). VEGF and KDR expression were evaluated in epithelial, stromal and endothelial compartments in order to identify autocrine and/or paracrine loops. In dogs an increased VEGF expression did not show any statistical correlation with the clinicopathological parameters examined and was not correlated to a poorer prognosis. MVD was found to be significantly correlated to the histologic type (P=0.04), tumour grading (P=0.02), and to the OS (P=0.01). In cats VEGF expression was significantly correlated to tumor grading (P=0.01) and OS (P=0.03), while no significant associations were found between MVD and the other parameters. VEGF and KDR were found to be detected on the epithelial, and/or endothelial and/or stromal cells of the carcinomas in both species, suggesting indications for some possible autocrine and paracrine loops. Our results encourage further studies on the possible prognostic role of VEGF and MVD in canine and feline mammary tumours and on the role of growth factors and their receptors in promoting tumour proliferation and an "angiogenetic shift". The VEGF/KDR system may play a role in malignant transformation and tumor progression.

Androgen receptor expression in normal, hyperplastic and neoplastic hepatoid glands in the dog.

Neoplasms of the perianal glands are common in the dog, particularly in the male. The occurrence of these tumours appears to be hormone related and castration, without excision of the tumour, has sometimes resulted in regression of the tumour. The aim of this study was to investigate the expression of androgen receptors (AR) in normal, hyperplastic and neoplastic hepatoid glands in the dog. Thirty-one samples of canine hepatoid gland tissues were investigated. The lesions, classified according to WHO criteria, were comprised of 19 hyperplastic tissues, 10 benign lesions (2 hepatoid gland epithelioma and 8 hepatoid adenomas), and 19 carcinomas. Five samples from normal hepatoid glands were also investigated. The AR expression was evaluated by immunohistochemistry using a streptavidin-biotin peroxidase method. The immunoexpression was scored by two pathologists as the percentage of positive nuclei. The intensity of staining was also considered. AR expression was detected in all normal and abnormal glands. However, in hyperplastic tissues the percentage of positive nuclei was significantly higher than in normal tissue and especially in reserve basaloid cells. A similar increase in the percent of positive nuclei was also observed in hepatoid epitheliomas, while in hepatoid adenoma the percent of AR-immunolabelling was only slightly increased compared to normal tissue. In hepatoid carcinomas the percent of AR-positive cells was similar to that observed in benign tumours. The grade of differentiation of hepatoid carcinomas did not affect AR expression. These results demonstrate that increased AR expression is maintained throughout perianal gland cancer progression and that hepatoid gland carcinomas still express AR. Although further studies may be required to evaluate the hormonal background of these diseases, dogs bearing those carcinomas might benefit from castration or anti hormonal therapy.

External quality assessment for the detection of blood-borne viruses in plasma by nucleic acid amplification technology: the first human immunodeficiency virus and hepatitis B virus studies (HIV EQA/1 and HBV EQA/1) and the fifth hepatitis C virus study (HCV EQA/5).

BACKGROUND AND OBJECTIVES: This External Quality Assessment (EQA) study was aimed at assessing the proficiency of blood centres and blood product manufacturers in detecting, by nucleic acid amplification technology (NAT), the possible contamination of plasma with hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV). MATERIALS AND METHODS: Three independent panels, one for each virus, were prepared at the Istituto Superiore di Sanità (ISS) by diluting the respective reference preparations. NAT methods used by the EQA participants included polymerase chain reaction (PCR) assays by Roche, transcription-mediated amplification (TMA) assays by Chiron and in-house PCR assays. RESULTS: Forty-three of the 45 participants (95.6%) in the HCV EQA/5 who used a validated method were consistently able to detect a nominal concentration of 100 IU/ml for all six major genotypes. In the case of the HIV EQA/1, all 35 participants detected the samples containing 1000 IU/ml HIV, while five (14.3%) did not identify the samples containing 100 IU/ml HIV. With respect to the HBV EQA/1, all 16 participants correctly identified the positive samples containing either 1000 IU/ml or 100 IU/ml HBV. No false-positive results were observed with any of the three panels. CONCLUSIONS: The HCV EQA/5 showed an improved proficiency of laboratories as compared with the HCV EQA/4. In fact, HCV genotypes 1, 2, 3 and 5 were correctly identified in 100% of the assays and genotypes 4 and 6 in 97.8% of the assays. While most of the participants in the HIV EQA/1 showed a good level of proficiency, an excellent performance was shown by all participants in the HBV EQA/1.

Involvement of mu class glutathione S-transferase subunit M2 (rGST M2) levels in the initiation and promotion of hepatocellular carcinogenesis in old rats.

Age-associated differences in the response of the initiation and promotion of hepatocellular carcinogenesis in the rat were analyzed. Male Wistar rats 5 and 18 months-old were used throughout. They underwent an experimental design of multistage model of hepatocarcinogenesis: hepatic cells were initiated with the complete carcinogen Aflatoxin B1 (0.5mg/Kg b.w.) and the promotion was performed through a combined treatment of proliferation (partial hepatectomy, 65%) and administration of the tumorigenic promoter phenobarbital (0.1% in drinking water for 21 days). After the treatment, rats were sacrificed and the following parameters were determined: activity and subunit composition of the glutathione S-transferase enzyme system, the number of liver preneoplastic foci and the proliferation cell index. The combined treatment (initiation + promotion) lowered the expression of the mu class GST (rGST M1, rGST M2). The inhibition in rGST M2 in old animals (which in basal conditions had already been lower) was significant. On the other hand, the treatment increased the alpha class GST (rGST A, rGST A3). The number of preneoplastic foci was higher in old rats (number of foci/cm(2): 6.9+/-0.3 vs 3.9+/-0.3 in young rats, p< 0.05). The proliferation cell index did not show age-related differences. Because rGST M2 deficiency coexisted with induced expression of alpha class, the livers would be resistant to some toxic insults, being selectively sensitive to potentially genotoxic substances for which M2 is an essential detoxification pathway. The transition to a rGST M2-deficient phenotype during aging could induce higher responsiveness to genotoxic effects, and might favor the likelihood of further progression, indicating a higher susceptibility of aged animals to the development of carcinogenesis.

[In vivo apoptotic effect of alpha-2b interferon (IFN) on rat preneoplastic liver ]. / Efecto apoptotico in vivo del interferon alfa-2b (IFN) sobre higados preneoplasicos de rata.

In order to know whether IFN alpha prevents in vivo oncogenesis in the very-early-stage cancer cells, we evaluated the action of IFN alpha-2b on preneoplastic foci in rats. Animals were divided into six groups: subjected to an initiation-promotion model of cancer development (G1), treated with IFN alpha-2b during: a) initiation-promotion (G2), b) initiation (G3), promotion (G4); subjected only to an initiation stage (G5) and treated with IFN alpha-2b during this period (G6). The number and area of rGST P-positive foci were reduced and the Apoptotic index was increased in G2, 3 and 6. Bcl-2 and Bcl-XL protein levels were decreased in IFN alpha-2b-treated rats. Increased levels of mitochondrial Bax protein were observed in G2, 3 and 6. In conclusion, preneoplastic hepatocytes in the IFN alpha-2b-treated rats undergo programmed cell death as a result of a significant increase of Bax and its translocation to the mitochondria.

HIV-HCV RNA loads and liver failure in coinfected patients with coagulopathy.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure contemporaneously HCV-RNA load, HIV-RNA load and CD4+ lymphocyte count in HCV/HIV coinfected patients with coagulopathy and to examine the relationship between these parameters and the liver failure. DESIGN AND METHODS: A cross-sectional study was performed on 54 patients with severe coagulopathy: 39 HCV/HIV coinfected and 15 HCV+/HIV- comparable for age and HCV exposure time. HCV-RNA and HIV-RNA load, CD4+ lymphocyte count, biochemical and ultrasonographic parameters were evaluated at the time of entry to the study. RESULTS: Mean HCV-RNA load was significantly higher in coinfected patients (643,872 717,687 copies/mL) than in HCV+/HIV- (mean 161,573 276,896 copies/mL) (p = 0.01). The 39 HCV/HIV coinfected patients had a mean HIV-RNA load of 205,913 456,311 copies/mL (range 4,000-2,500,000) and a mean CD4+ lymphocyte count of 206.5171/microL (range 5-693). Five of the 39 (12.8%) coinfected patients had liver failure. In these five patients the mean HCV-RNA load (770,200 996,426 copies/mL) was high but not significantly different from that in the 34 HCV+/HIV+ patients (623,496 682,239 copies/mL) without liver failure (p = 1.0). Coinfected patients with liver failure had a significantly higher HIV-RNA load (mean 764, 599 978,542 copies/mL) and lower CD4+ lymphocyte count (mean 52.655. 6/microL) than those observed in coinfected patients without liver failure (p = 0.007 and p = 0.03, respectively). A significant inverse correlation was found between CD4+ lymphocyte count and HIV-RNA load (r = -0.37, p = 0.01). INTERPRETATION AND CONCLUSIONS: HCV-RNA load is significantly higher in HIV+ than in HIV- patients with coagulopathy. Liver failure was found only in the HCV/HIV coinfected patients with severe immunodepression, expressed either by low CD4+ lymphocyte count or by high HIV-RNA load.

[Hysteroscopic features in postmenopausal uterine bleeding]. / Quadri isteroscopici nei sanguinamenti uterini in post-menopausa.

One hundred forty three patients underwent hysteroscopy for abnormal uterine bleeding from January 1993 through December 1994. Sixty patients were postmenopausal. All but 3 of the procedures were performed on outpatient with no significant complications. Three groups could be identified on the basis of endometrial features (color, vascularity, thickness, necrotic areas): 1) negative for cancer, 2) possible or suspect (low or high risk), 3) carcinoma. Biopsy indicated cancer in one of the 16 doubtful cases, and in all (5) of the hysteroscopically diagnosed cancers. Outpatient Hysteroscopy successfully substitutes D&C (dilatation and curettage) for early diagnosis of endometrial cancer.

Rapidly progressive squamous cell carcinoma of the cervix in a patient with acquired immunodeficiency syndrome: case report.

Recent evidence suggests an association between cervical condyloma, dysplasia and HIV infection. However, the course of cervical cancer in immunodeficient patients has not yet been thoroughly researched. Cervical cancer presently amounts to 1% of the causes of death in AIDS patients. This percentage is bound to increase not only because an improved life expectancy has been obtained, but mainly because the virus is widely spreading among the female population. A 28 year-old AIDS patient, parity 1/0/1/1, underwent gynecological examination and colposcopy following an episode of vaginal bleeding. Biopsy revealed an invasive cervical carcinoma. The last gynecologic investigation, which included a Pap smear and colposcopy, was performed 14 months earlier and resulted negative. Cytologic reexamination of the specimen confirmed the previous Pap smear result. Proctoscopy and cystoscopy showed no mucose involvement. Urography was negative. The cat scan indicated minor spleen and liver enlargement but no signs of malignant abdominal spread were found. The neoplasia was classified as a stage IIB cervical carcinoma (according to the FIGO classification) due to the spread to the left cardinal ligament. In spite of radiation therapy, the disease rapidly progressed leading to a monolateral ureteral involvement which created a juxtavescical stenosis. The patient died three months later. Necroscopic examination revealed lung metastasis. Such a rapidly progressive form of cervical cancer could be related to the acquired immunodeficiency condition. Recurrent cytological and colposcopic examinations are to be considered mandatory in HIV patients.

Recombinant expression of hepatitis A virus protein 3A: interaction with membranes.

The function of hepatitis A virus (HAV) protein 3A and its structural requirements were studied in vitro and in a bacterial expression system by comparing the polypeptide precursor 3AB derived from a cytopathogenic strain with that of an attenuated strain. Although the precursor polypeptides 3AB of both HAV strains bind to microsomal membranes after translation in vitro they differ in inducing membrane permeability when expression is induced in bacteria. Intake and release of macromolecules was dramatically increased when 3AB of the cytopathogenic strain was expressed. Amino acid sequence alignments suggest that membrane binding might be due to a hydrophobic stretch near the C-terminus of 3A found in all picornaviruses whereas the ability to induce permeability of E. coli membranes is determined by an amphipathic helix formed at the N-terminus of 3A of HAVFG.

Mutations in the 3A genomic region of two cytopathic strains of hepatitis A virus isolated in Italy.

Two strains of hepatitis A virus (HAV) were isolated in cell culture and found to induce a cytopathic effect at early passages. The nucleotide sequences of the 5' non-translated region (5'NTR) and of genes 2B, 2C, 3A and 3B were determined for these strains and found to contain mutations similar to those detected in cell-culture adapted variants of HAV strain HM175. In addition, gene 3A shows a deletion of three aspartic acid residues near the N-terminus of the polypeptide. In combination with variations in the 5'NTR and in genes 2B and 2C, the absence of an aspartic acid residue in position 4 of gene 3A of three cytopathic clones of HM175 suggests a possible role of the 3A protein in determining the cytopathic phenotype.