PubMed Health⌕ Search

Biomedical subjects

D Moro

Publications and source records attributed to D Moro.

At least 19 recordsLinked to original sources

A solid state microdosimeter based on a monolithic silicon telescope.

A monolithic silicon telescope, consisting of a DeltaE and an E stage-detector ( approximately 1.9 microm and 500 microm thick, respectively), was coupled to a polyethylene converter in order to investigate the feasibility of a solid state microdosimeter with respect to the field-funnelling effect. This work discusses the preliminary results of an analytical approach for the correction of a spectrum measured with this silicon-based microdosimeter for tissue-equivalence and geometrical effects. The device was irradiated with 2.7 MeV monoenergetic neutrons at the INFN-Laboratori Nazionali di Legnaro (Legnaro, Italy). The non tissue-equivalence of silicon was corrected by exploiting the signals generated in the E-stage. The correction for the sensitive volume geometry was optimised by taking into account the track length distribution of the recoil-protons generated in the converter. The derived dose distribution of the energy imparted per event was compared to the one measured with a cylindrical tissue-equivalent proportional counter (TEPC). The agreement is satisfactory.

Computer-Aided Design↗

Effect of a 3-week body mass reduction program on body composition, muscle function and motor performance in pubertal obese boys and girls.

The aim of this study was to investigate the effects of a multidisciplinary body mass reduction (BMR) program on body composition, muscle function and motor performance in 50 obese [mean body mass index (BMI): 35.9+/-5.8 kg/m2] boys and girls aged 12-17 yr (Tanner stage III, IV and V). The hospital-based BMR program combined an energy-restricted diet (1400-1600 kcal), nutritional education, psychological counselling and moderate physical activity (45-60 min/ session; 5 sessions/week; 60-80% of the maximal heart rate) during a 3-week period. Fat mass, fat-free mass, maximal power during jumping and stair climbing as well as maximal strength of the upper and lower limb muscles were quantified before and after the treatment. Body mass and fat mass significantly decreased following the BMR program, respectively -5.1 and -7.8% (p<0.001), while percent fat-free mass increased 2.3% (p<0.001). The treatment significantly increased both stair climbing and jumping power, respectively 8.2 and 8.9% (p<0.05), and the same was true for maximal strength of the upper and lower limb muscles (p<0.001). For the first time, it was demonstrated that a BMR program entailing diet and physical exercise significantly improved body composition, muscle function and motor performance in obese boys and girls aged 12-17 yr, while gender and pubertal stages had no influence on BMR program-induced changes.

Adolescent↗

E-cadherin-beta-catenin adhesion complex in neuroendocrine tumors of the lung: a suggested role upon local invasion and metastasis.

Dysfunction or loss of the intercellular adhesion complex E-cadherin-beta-catenin is frequent in non-small cell lung carcinomas in which E-cadherin and beta-catenin loss has been considered to be a molecular marker of tumor progression and poor prognosis. With an aim of evaluating the expression of the E-cadherin-beta-catenin complex and its prognostic role in neuroendocrine tumors (NET) of the lung, immunohistochemical analysis was performed in 102 NET, including 16 low-grade typical carcinoids, 8 intermediate-grade atypical carcinoids, 37 large-cell neuroendocrine carcinomas (LCNEC), and 41 small-cell lung carcinomas, both high-grade tumors. Impaired E-cadherin expression (loss or cytoplasmic delocalization) was observed in 80 (78%) of 102 samples, and impaired beta-catenin expression was noted in 74 (72%) of 102 cases. The impaired expression of E-cadherin and beta-catenin was observed with a higher frequency in high-grade tumors (87% and 83%, respectively) than in carcinoids (50% and 37%, respectively; P < 0.0001). Impaired expression of the E-cadherin and beta-catenin molecules also correlated with lymph node metastasis (P = 0.0001 and P = 0.0005, respectively) and with advanced stage disease (P < 0.0001 for both factors). Moreover, impaired E-cadherin expression directly correlated with an extensive disease in carcinoids and in LCNEC (P = 0.02 and P = 0.04, respectively) and with node metastasis in LCNEC (P = 0.01). Levels of E-cadherin and beta-catenin were correlated with each other, consistent with an internal regulatory loop. Our results indicate that down-regulation of the E-cadherin-beta-catenin complex plays a role in NET progression.

Cadherins↗

Microdosimetric investigation at the therapeutic proton beam facility of CATANA.

Proton beams (62 Mev) are used by the Laboratori Nazionali del Sud of the Italian Institute of Nuclear Physics to treat eye melanoma tumours at the therapeutic facility called CATANA. A cylindrical slim tissue-equivalent proportional counter (TEPC) of 2.7 mm external diameter has been used to compare the radiation quality of two spread-out Bragg peaks (SOBP) at the CATANA proton beam.

Algorithms↗

Pathogens of house mice on arid Boullanger Island and subantarctic Macquarie Island, Australia.

Studies on island populations of house mice (Mus domesticus) and their viruses reveal insights into viral persistence in isolated communities. We surveyed the ectoparasites, endoparasites, and antiviral antibodies for 11 murine viruses and two bacteria of house mice inhabiting two islands off Australia. House mice on Boullanger Island were seropositive to two viruses, murine cytomegalovirus and epizootic diarrhea of infant mice. On subantarctic Macquarie Island, house mice were seropositive for five viruses: murine cytomegalovirus, lymphocytic choriomeningitis virus, mouse parvovirus, epizootic diarrhea of infant mice, and Theiler's murine encephalomyelitis virus. The diversity of antiviral antibodies was lower among populations of house mice on islands than those inhabiting mainland Australia. The decreased diversity of viruses in island populations of house mice may be a function of which agent the founder mice transfer to the island and related to the low densities which the host population may periodically reach over time.

Animals↗

Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study.

BACKGROUND: The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE). METHODS: In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided. RESULTS: Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment. CONCLUSION: Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.

Adult↗

Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test.

OBJECTIVE: The aim of this study was to evaluate liver steatosis in prepubertal and pubertal obese and the correlations with the lipid profile, the serum levels of hepatic parameters and the glycemic and insulinemic responses to an oral glucose tolerance test. SUBJECTS: 375 obese, 205 males and 170 females, Tanner pubertal stage I (n=82), stages II-III (n=80) and stages IV-V (n=213). MEASUREMENTS: Body mass index (BMI), waist-hip ratio (WHR), total cholesterol and high density lipoprotein (HDL), cholesterol/HDL ratio, low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides (TGL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gGT, glycemia (G), insulinemia (IRI), fasting IRI/G ratio (FIGR), glycemic (mean blood glucose, MBG) and insulinemic (mean serum insulin, MSI) responses during a 120 min oral glucose tolerance test (OGTT), expressed as area under the curve (AUC)/120 min, pancreatic insulinemic response to glucose (IRG), and liver ultrasound scanning for assessing the degree of steatosis (moderate, severe). RESULTS: Liver steatosis was found in 33% of subjects in Tanner pubertal stage I, 36% in stage II-III and 47% in stages IV-V. BMI and transaminases were correlated with the degree of steatosis in all pubertal stages. AST, ALT and gGT were higher in the presence of steatosis, while elevated TGL was present in late puberty only; however the increase of ALT is specific for steatosis. CONCLUSION: Juvenile obesity involves a high risk of liver steatosis associated with alterations of transaminases and lipid but not glucose metabolism. These changes are apparent even to the prepubertal stage.

Alanine Transaminase↗

NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas.

Neural cell adhesion molecules (NCAM) are adhesion molecules expressed by neural and neuroendocrine tumors and a few biphasic tumors such as synovialosarcomas and breast phyllode tumors. To investigate NCAM expression in mesotheliomas, we studied 26 cases of epithelioid (n = 12), biphasic (n = 11), and sarcomatoid (n = 3) malignant mesotheliomas (MM), in comparison with normal mesothelium, and 50 primary non-small cell lung carcinomas (NSCLC) (25 adenocarcinomas [ADC] and 25 squamous cell carcinomas [SCC]), using electron microscopy as a gold standard for recognition of MM. NCAM reactivity using 123C3 antibody was compared with that of NE markers such as chromogranin A and synaptophysin. Although normal mesothelium remains negative, NCAM was expressed in 19 of 26 MM (73%) with a membranous staining on frozen or paraffin sections. In 6 of 12 epithelioid MM, the tumor cells expressed NCAM, whereas in 5 cases stromal fibroblasts showed a strong but focal staining. In 11 biphasic MM, 4 presented an NCAM reactivity of both epithelioid and spindle cell components, whereas in 7, only fusiform component was NCAM positive. Two of 3 sarcomatoid MM showed an NCAM expression. Chromogranin expression was never seen, whereas synaptophysin was noticed in 2 cases. No case of NSCLC showed membranous 123C3 staining, whereas 2 ADC weakly expressed synaptophysin. We conclude that NCAM expression in MM is reminiscent of its expression in mesoderm during fetal life and consistent with that reported in other biphasic tumors. These data show that NCAM expression occurs in 73% of MM, highly exceeding that observed in lung cancer.

Adenocarcinoma↗

Phase II trial of up-front accelerated thoracic radiotherapy combined with chemotherapy and optional up-front prophylactic cranial irradiation in limited small-cell lung cancer. Groupe d'Oncologie Thoracique des Régions Alpines.

PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m(2) for 3 days and cisplatin 25 mg/m(2) for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m(2) dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.

Adult↗

[Iodine deficiency in the Federation of Bosnia and Herzegovina].

Iodine deficiency which causes the wide spectrum of disorders for all ages, is one of the significant public health problem worldwide. From the ancient times different iodine deficiency disorders were noticed in Bosnia and Herzegovina and in its some areas the goiter existed in endemic form. These facts confirm that its soil bas been iodine deficient and that necessity for iodine prophylaxis is obvious on its territory. The study was based on 5,523 children, of both sex boys and girls school age from 7 to 14 years, randomly selected with the equal participate subjects in relation to the age. The sample is representative and it has been assessed based on: total number of school children aged from 7 to 14 years, anticipated prevalence of goiter 5% level of probability 95%, relative punctuality 30% and the factor called "design effect" which is 3. The study was carried out in whole ten cantons in the schools with equal representation among cities and villages. In examining of prevalence of giter we used inspection and palpation. Determination of iodine concentration in urine was carried out by the method is based on Sandel-kolthof's reaction. The technique used for determination of concentration of iodine in salt was iodinemetric titration. The prevalence of goiter was 27.6% in Federation of Bosnia and Heryegovina. The highest prevalence of goiter was in Bosnia Podrinje Canton (51.20%) while the lowest was in West Herzegovina Canton (12.90%). The urinary iodine excretion in investigated children varied from 1 to 208 *mg/L with median of 77.6 *mg/L. Iodine contetn in household salt samples was from 3 to 29.8 mg/kg, range 14.4 + 5.9 mg/kg. The results of our study show the persistence of mild to moderate iodine deficiency in Bosnia and Herzegovine Federation. Therefore according to the recommendations of the World Health Organisation, UNICEF and International Council for Control of Iodine Deficiency Disorders, the salt for human, and animal consumption as well as for food industry which is consuming on its teritory, has to be iodinated on the place of its production without looking back whether or not it is produced or imported in Bosnia and Herzegovina Federation, lodination has to be performed with 20 to 30 mg KI per one kg of salt, thereby an average the iodine content has to be 25 mg per kg. In this way it will be prevented the wide spectrum of disorders, which we often are not aware for that its are caused by iodine deficiency. In addition it will be prevented many very important socioeconomical consequences of iodine deficiency.

Adolescent↗

Alterations of expression of Rb, p16(INK4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance.

Inactivation of the Rb pathway in non-small cell lung carcinoma (NSCLC) occurs mostly through inactivation of the cyclin-dependent kinase inhibitor p16(INK4A) and/or up-regulation of cyclin D1. In order to assess the frequency and the prognostic value of these abnormalities in NSCLC, immunohistochemical analysis of Rb, p16(INK4), and cyclin D1 has been performed on 168 cases of NSCLC including 77 squamous cell carcinomas, 43 adenocarcinomas, and 48 basaloid carcinomas. The reduced survival rate of basaloid carcinoma (stage I-II) compared with other histological types of NSCLC was confirmed (p = 0.008). Loss of protein expression of Rb and p16(INK4A) was observed in 12 per cent and 58 per cent of NSCLC cases respectively and cyclin D1 overexpression in 43 per cent. There was an inverse correlation between Rb and p16 expression ( p < 0.0001) and a direct correlation between Rb and cyclin D1 expression ( p = 0.0007). In univariate analysis, Rb-negative adenocarcinomas at stages I-II had a significantly shorter survival than Rb-positive cases ( p = 0.04) and stages I-II p16-positive cases had a shorter survival than p16-negative cases ( p = 0.02), which was more significant in basaloid carcinoma ( p = 0.003). p16 status retained its influence on survival in multivariate analysis at stage I-II for all cases ( p = 0.01) and for basaloid carcinoma ( p = 0.005). Cyclin D1 overexpression did not influence survival. Combined Rb/p16/cyclin D1 phenotypes in univariate analysis showed a shorter survival for Rb-negative/p16-positive/cyclin D1-negative tumours ( p = 0.002). These results, linked to previous data, indicate that the Rb pathway of G1 arrest is initially disrupted in the vast majority of NSCLCs (83 per cent), but could not confirm an unfavourable role for each individual event (p16(INK4A) loss or cyclin D1 up-regulation) in prognosis.

Adenocarcinoma↗

Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival.

The formation of new vessels (angiogenesis) is essential for primary tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). The microvascular density (MVD) in tumours was assessed and the expression of VEGF and its receptors VEGF-R1-Flt1 and VEGF-R2-KDR/Flk1 was investigated in the different cellular compartments in vivo, in order to establish their interrelationship and their prognostic influence. Immunohistochemical study of 69 stage I-II non-small cell lung carcinomas (NSCLCs) was performed on paraffin sections with CD34 antibody to estimate MVD, using a Chalkley eye-piece graticule and VEGF, VEGF-R1, and VEGF-R2 antibodies. There was strong expression of VEGF and its receptors in tumour cells, endothelial cells, and stromal fibroblasts. In tumour cells, the level of VEGF was correlated with that of VEGF-R1 ( p = 0. 018) but not that of VEGF-R2. In fibroblasts, high expression of VEGF was correlated with that of VEGF-R1 ( p = 0.0001) and VEGF-R2 ( p = 0.0001). In endothelial cells, expression of VEGF was correlated with that of VEGF-R1 ( p < 0.0001) and VEGF-R2 ( p = 0.04). The level of VEGF in fibroblasts was correlated with that of VEGF-R1 ( p = 0.0028) and VEGF-R2 ( p = 0.01) in endothelial cells. There was no correlation between the level of MVD and that of VEGF or VEGF-R1 or VEGF-R2. Neither the level of MVD, nor the level of expression of VEGF and VEGF receptors in any compartment influenced the patient's survival. In conclusion, although angiogenesis is essential for tumour growth, this study failed to demonstrate that MVD, VEGF, VEGF-R1, and VEGF-R2 are prognostic markers for stage I-II NSCLC. VEGF, however, might act as a direct autocrine growth factor for tumour cells via VEGF-R1 and angiogenesis could be promoted in a paracrine loop, where VEGF is produced by fibroblasts and tumour cells and then binds to endothelial cells via induced VEGF receptors. VEGF and its receptors thus appear as relevant therapeutic targets in NSCLC.

Adenocarcinoma↗

Endovascular treatment of superior vena cava obstruction in patients with malignancies.

The aim of this study was to report our experience on the management of superior vena cava obstruction (SVCO) secondary to malignant disease, using endovascular procedures. Twenty-six patients with SVCO due to primary or secondary tumors of the lung or the mediastinum, or catheter inserted for treatment of an extra-thoracic neoplasm, had an endovascular therapy which consisted of stenting, angioplasty, thrombo-aspiration or local fibrinolysis. Immediately after the procedure, rapid relief of symptoms occurred in 24 (90 %) of the patients. The mean Kishi's score decreased from 5.5 to 0.96. Immediate complications included one death related to pericarditis bleeding following fibrinolysis. Three patients relapsed after 20 days, 4 months and 6 months, and needed a second stenting. At 6 months the primary patency rate was 83 % and the secondary patency rate was 89 %. Endovascular treatment of SVCOs is a simple and safe procedure to restore the patency of the superior vena cava in malignant SVCO. It should be indicated in most cases as first-line treatment and performed as early as possible.

Adult↗

Water and sodium requirements of field populations of house mice (Mus domesticus) and short-tailed mice (Leggadina lakedownensis) on Thevenard Island, in the arid Pilbara region of Western Australia.

The coexistence of the Lakeland Downs short-tailed mouse Leggadina lakedownensis and house mouse Mus domesticus on Thevenard Island, in the arid north of Western Australia, prompted a study to compare their seasonal water and sodium metabolism using tritiated water and sodium-22 as tracers. Fractional water influx rates for M. domesticus (40.3 +/- 1.6% total body-water day-1) were significantly higher than those for L. lakedownensis (25.3 +/- 1.2% total body-water day-1). Water effluxes were higher in both species of mouse after the passage of a cyclonic storm near the study site. Water flux differences remained significant between species when turnover rates were scaled with body mass. A comparison of water influx rates of M. domesticus with those predicted for field populations of other eutherian rodents showed that rates for M. domesticus on Thevenard Island were higher than expected. In contrast, water influx rates for L. lakedownensis did not differ significantly from expected values for a desert rodent. Rates of sodium influx for M. domesticus (41.7 +/- 3.6 mmol kg-1 day-1) were over twice those of L. lakedownensis (19.7 +/- 4.8 mmol kg-1 day-1), and were reflected in the significantly higher concentrations of sodium ingested in the diet, and excreted in the urine, of M. domesticus. Furthermore, the rate of water influx was positively correlated with the rate of sodium influx in M. domesticus, suggesting that they were obtaining both water and sodium from the one dietary source. There was no evidence to suggest that mice of either species were experiencing water or sodium stress, because water and sodium influxes and effluxes remained in balance. These results suggest that M. domesticus on Thevenard Island had a higher-than-expected daily water requirement, and may represent a mesic deme of house mice that have yet to adapt to the island environment.

Animals↗

Water and sodium balances and metabolic physiology of house mice (Mus domesticus) and short-tailed mice (Leggadina lakedownensis) under laboratory conditions.

A laboratory study investigated the metabolic physiology, and response to variable periods of water and sodium supply, of two arid-zone rodents, the house mouse (Mus domesticus) and the Lakeland Downs short-tailed mouse (Leggadina lakedownensis) under controlled conditions. Fractional water fluxes for M. domesticus (24 +/- 0.8%) were significantly higher than those of L. lakedownensis (17 +/- 0.7%) when provided with food ad libitum. In addition, the amount of water produced by M. domesticus and by L. lakedownensis from metabolic processes (1.3 +/- 0.4 ml.day-1 and 1.2 +/- 0.4 ml.day-1, respectively) was insufficient to provide them with their minimum water requirement (1.4 +/- 0.2 ml.day-1 and 2.0 +/- 0.3 ml.day-1, respectively). For both species of rodent, evaporative water loss was lowest at 25 degrees C, but remained significantly higher in M. domesticus (1.1 +/- 0.1 mg H2O.g-0.122.h-1) than in L. lakedownensis (0.6 +/- 0.1 mg H2O.g-0.122.h-1). When deprived of drinking water, mice of both species initially lost body mass, but regained it within 18 days following an increase in the amount of seed consumed. Both species were capable of drinking water of variable saline concentrations up to 1 mol.l-1, and compensated for the increased sodium in the water by excreting more urine to remove the sodium. Basal metabolic rate was significantly higher in M. domesticus (3.3 +/- 0.2 mg O2.g-0.75.h-1) than in L. lakedownensis (2.5 +/- 0.1 mg O2.g-0.75.h-1). The study provides good evidence that water flux differences between M. domesticus and L. lakedownensis in the field are due to a requirement for more water in M. domesticus to mect their physiological and metabolic demands. Sodium fluxes were lower than those observed in free-ranging mice, whose relatively high sodium fluxes may reflect sodium associated with available food.

Animals↗

Murine viruses in an island population of introduced house mice and endemic short-tailed mice in Western Australia.

House mice (Mus domesticus) were recently introduced to Thevenard Island, off the northwest coast of Western Australia. This island is also habitat for an endangered native rodent, the short-tailed mouse (Leggadina lakedownensis). Concerns have been raised that house mice may pose a threat to L. lakedownensis both through competition and as a source of infection. To assess the threat to L. lakedownensis posed by viral pathogens from M. domesticus, a serological survey was conducted from 1994 to 1996 of both species for evidence of infection with 14 common murine viruses (mouse hepatitis virus, murine cytomegalovirus, lymphocytic choriomeningitis virus, ectromelia virus, mouse adenovirus strains FL and K87, minute virus of mice, mouse parvovirus, reovirus type 3, Sendai virus, Theiler's mouse encephalomyelitis virus, polyoma virus, pneumonia virus of mice, and encephalomyocarditis virus) and Mycoplasma pulmonis. Despite previous evidence that populations of free-living M. domesticus from various locations on the Australian mainland were infected with up to eight viruses, M. domesticus on Thevenard Island were seropositive only to murine cytomegalovirus (MCMV). Antibodies to MCMV were detected in this species at all times of sampling, although seroprevalence varied. Infectious MCMV could be isolated in culture of salivary gland homogenates from seropositive mice. In contrast, L. lakedownensis on Thevenard Island showed no serological evidence of infection with MCMV, any of the other murine viruses, or M. Pulmonis, and no virus could be isolated in culture from salivary gland homogenates. Although MCMV replicated to high titers in experimentally infected inbred BALB/c laboratory mice as expected, it did not replicate in the target organs of experimentally inoculated L. lakedownensis, indicating that the strict host specificity of MCMV may prevent its infection of L. lakedownensis. These results suggest that native mice on Thevenard Island are not at risk of MCMV infection from introduced house mice, and raise interesting questions about the possible selective survival of MCMV in small isolated populations of M. domesticus.

Animals↗

Alterations of Rb pathway (Rb-p16INK4-cyclin D1) in preinvasive bronchial lesions.

Lung cancer results from a stepwise accumulation of genetic and molecular abnormalities with unknown temporal relationships to precursor bronchial lesions. In a search for biomarkers of malignant progression, we analyzed the expression of the tumor suppressor gene Rb and of the proteins regulating its phosphorylation and function in G1 arrest, p16INK4A and cyclin D1, in preinvasive bronchial lesions accompanying cancer in 75 patients, in comparison with similar lesions in 22 patients with no cancer history. Rb was constantly expressed in preinvasive lesions, including carcinoma in situ (CIS). In contrast, p16 expression was lost in moderate dysplasia (12%) and in CIS (30%) in patients with lung cancer. p16 loss occurred exclusively in patients who displayed loss of p16 expression in their related invasive carcinoma. Loss of p16 expression was not seen in nine patients with dysplasia but no cancer progression. Cyclin D1 overexpression was seen in hyperplasia and metaplasia (6%), mild dysplasia (17%), moderate dysplasia (46%), and CIS (38%) in patients with cancer but was lost in 5% of the patients during the process of invasion; it was also observed in patients with no cancer progression (14%). Our results indicate that Rb protein function can be invalidated before invasion through alteration of the Rb phosphorylation pathway, by p16 inhibition, and/or by cyclin D1 overexpression and suggest a role for p16 and cyclin D1 deregulation in progression of preinvasive bronchial lesions to invasive carcinoma.

Biomarkers, Tumor↗