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Biomedical subjects

D Gallo

Publications and source records attributed to D Gallo.

At least 19 recordsLinked to original sources

Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy.

This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.35% or 0.7% of soy extract. Treatment started at weaning and continued to the end of the study (24 weeks after DMBA administration). At day 50 of age all animals received via oral gavage 80 mg/kg DMBA. Only tumors subsequently classified as adenocarcinomas were considered for data evaluation. In rats on the soy diet, mammary tumors took a longer period of time to develop as compared to control rats. However, at the end of the study, no relevant difference in tumor incidence and multiplicity was observed among the groups. The most significant changes were seen between control and soy-treated groups when tumor dimension and results from histopathologic examination were considered. The latter, in fact, showed a dose-dependent reduction in the percentage of poorly differentiated tumors in treated animals. This change was statistically significant in animals receiving 0.7% soy. In addition, assessment of estrogen and progesterone receptor (ERalpha, PR) levels, revealed a significant reduction in the percentage of ERalpha and PR positive tumors in animals receiving 0.7% dietary soy, when compared to controls. Interestingly, genistein and daidzein plasma levels determined at the end of the study were within the range of those detected in people consuming large amounts of soyfoods.

9,10-Dimethyl-1,2-benzanthracene↗

Characterization of two new alleles at the goat CSN1S2 locus.

Two novel alleles at the goat CSN1S2 locus have been identified: CSN1S2(F) and CSN1S2(D). Sequence analyses revealed that the CSN1S2(F) allele is characterized by a G --> A transition at the 13th nucleotide in exon 3 changing the seventh amino acid of the mature protein from Val to Ile. The CSN1S2(D) allele, apparently associated with a decreased synthesis of alpha s2-casein, is characterized by a 106-bp deletion, involving the last 11 bp of the exon 11 and the first 95 bp of the following intron. Methods (PCR-RFLP and PCR) for identification of carriers of these alleles have been developed.

Alleles↗

Anti-tumour activity of a panel of taxanes toward a cellular model of human cervical cancer.

Using a model of human cervical cancer (ME-180 cells), the anti-tumour activity of paclitaxel was compared to that of docetaxel and IDN5109, a newly developed taxane. The growth inhibition effect of taxanes was assessed after 3 days of exposure. DNA analysis, the taxane-dependent modulation of the expression of the alpha and beta subunits of tubulin and DNA fragmentation were assessed by flow cytometry. The presence of apoptosis was confirmed by morphological analysis using a laser scan cytometer. For the evaluation of "in vivo" anti-tumour activity, taxanes were administered to nude mice intravenously once daily, according to a q3/4d x 4 schedule. Docetaxel, IDN5109 and paclitaxel obtained "in vitro" IC(50) values of 0.86, 1.4 and 2.4 nM, respectively. DNA analysis demonstrated a transient block at the G(2)/M phase of the cell cycle only after 12 h of culture in the presence of taxanes and an increase of nuclear fragmentation suggestive for apoptosis after additional 12 and 60 h of exposure. Morphological analysis confirmed the presence of apoptosis. Taxanes induced a down-modulation of the alpha subunit of tubulin in the G(0/1) phase of the cell cycle, and an overexpression of the beta subunit in the G(2)/M phase. A strong anti-tumour activity was obtained "in vivo" for nude mice xenografted using ME-180 cells (T/C=0% for all drugs). These data indicate that the three taxanes are strongly active both "in vitro" and "in vivo" toward ME-180 cells. Clinical studies are now needed to ascertain if the higher anti-tumour activity observed "in vitro" using docetaxel and IDN5109 yields a better clinical response in advanced cervical carcinoma with respect to paclitaxel.

Animals↗

Electrophoretic karyotyping and triazole susceptibility of Candida glabrata clinical isolates.

A series of 35 strains of Candida glabrata isolated from 29 subjects (5 AIDS patients and 24 HIV-seronegative individuals) were typed by electrophoretic karyotyping and tested for their susceptibilities to both fluconazole and itraconazole. Almost every individual harboured his/her own specific isolate (DNA type). Neither the source of isolation nor the patient's HIV status was associated with a given DNA type. Recurrences were generally due to the persistence of the same DNA type over time. Only 9% of the isolates showed reduced susceptibility to fluconazole (MIC > or = 8.0 microg/ml), while 43% of the isolates showed reduced susceptibility to itraconazole (MIC > or = 0.25 microg/ml) (P = 0.02). These data show that electrophoretic karyotyping is a useful technique for DNA typing of isolates of Candida glabrata. Care must be taken prior to initiation of antifungal therapy with either of these drugs.

Antifungal Agents↗

Reproductive effects of dietary soy in female Wistar rats.

This study was designed to assess the effects of administration of dietary soy on reproductive function and fertility of female Wistar rats. Four groups, each of 20 females, were used. Control animals were fed a standard cereal-based diet for rats. Treated animals were fed a standard diet supplemented with 0.7%, 1.2% or 2.4% of a soy extract. Treatment started at weaning and continued until day 7 post-partum (day of sacrifice). Growth depression was seen in the 2.4% soy group. Vaginal opening occurred earlier in females receiving soy supplemented feed when compared with controls. Analysis of vaginal smears revealed that all animals were cycling, although an increase in the mean duration of each cycle was seen in the 2.4% soy group. Uterine effects were observed in high-dose females and included increases in weight, oedema, endothelial hyperplasia and leucocytic infiltration. Vaginal modifications (i.e. inflammation, hyperkeratosis and dyskeratosis) and alterations in the distribution of follicular size in the ovaries were also observed among treated animals. These data suggest that long-term exposure to high doses of phytoestrogens can produce significant agonistic actions in several oestrogen-dependent tissues and parameters, even though in this model no clear influence on reproductive processes was observed.

Animals↗

In-vitro interactions of itraconazole with flucytosine against clinical isolates of Cryptococcus neoformans.

Treatment failures can occur in AIDS patients infected with Cryptococcus neoformans, despite aggressive antifungal therapy. Combination regimens with additive or synergic drugs could provide additional options for treating cryptococcosis. We studied the effects of itraconazole combined with flucytosine against 16 strains of C. neoformans var. neoformans. Combination therapy revealed different results for the various strains, including synergy (fractional inhibitory concentration (FIC) index 0.5, 63% of the interactions), addition (FIC >0.5 to 1.0, 31% of the interactions) and indifference (FIC >1.0 to <2.0, 6% of the interactions). Antagonism (FIC >2.0) was not observed. The efficacy of combination therapy was confirmed by quantitative cfu and killing curve assays. In particular, killing curves conducted in replicating cells showed that the addition of itraconazole prevented the development of flucytosine-resistant mutants of C. neoformans. These data show that the combination of itraconazole and flucytosine is significantly more active than either drug alone against C. neoformans in vitro.

Antifungal Agents↗

HTLV-1 infection in a population-based cohort of older persons in Guinea-Bissau, West Africa: risk factors and impact on survival.

In 1989, a population-based cohort of persons aged > or = 50 years was established in an urban area of Guinea-Bissau, West Africa. Overall, 346 persons were interviewed in detail about risk behaviors and had capillary blood drawn. Among women, 12.4% were HTLV-1 seropositive, compared with 4.6% in men. No HTLV-2 was found. Seropositivity varied considerably according to place of birth and ethnic group. In women, but not in men, HTLV-1 seropositivity was strongly associated with early sexual debut (10-14 yrs, 33.3%; 15-17 yrs, 26.0%; 18-20 yrs, 6.5%; 21+ yrs, 0%; ptrend = 0.001), lifetime number of male partners (ptrend = 0.006), and the male partner's number of co-wives (ptrend = 0.006). There was also a 3.1-fold increased risk of being HTLV-1 seropositive if the woman was also HIV-2 seropositive. In a multivariate-risk-factor analysis, the strongest association with HTLV-1 was a history of having been bitten by a monkey (n = 11; combined OR adjusted = 10.1; 95% CI 2.3-44.4). Ornamental scarification was associated with a 3.3-fold increased risk. Ethnic affiliation also significantly influenced the risk of being HTLV-1 seropositive. Follow-up performed in January 1996 revealed no difference in survival between HTLV-1-seropositive and -seronegative individuals over 6 years (rate ratio = 1.4, 95% CI 0.7-2.8). In conclusion, this population, which has very high HIV-2 seroprevalence, is also highly endemic for HTLV-1. Whereas sexual behaviors are clearly important for HTLV-1 spread in women, non-sexual risk factors were the only ones of potential importance in men. HTLV-1 had no impact on survival in this older population.

Aged↗

Antitumor activity of paclitaxel (taxol) analogues on MDR-positive human cancer cells.

A series of newly developed paclitaxel analogues have been tested for their growth inhibitory activity on two human breast cancer cell lines, one of which expresses the MDR (multidrug resistance) phenotype. Paclitaxel (taxol) was used as a reference compound. Three new classes of taxanes were analyzed: the cephalomannine compounds, the pyrazoline derivatives and the seco-derivatives. Our results demonstrated an increased antiproliferative activity of pyrazoline derivatives on drug-resistant cancer cells with respect to paclitaxel. These compounds were able to block MDR-bearing MCF-7 ADRr cells in the G2/M phase of cell cycle and, consequently, induce programmed cell death. In keeping with the antiproliferative effects, cells treated with paclitaxel derivatives showed a more pronounced cell cycle arrest than the parent compound paclitaxel. Also, apoptotic cell death, calculated as a percent of DNA fragmentation, occurred to a greater extent in cells exposed to pyrazoline derivatives. The development of new paclitaxel analogues with greater antitumour activity on MDR-positive cells may be useful in selecting new taxanes effective on resistant tumors.

Antineoplastic Agents, Phytogenic↗

Evaluation of a system using oral mucosal transudate for HIV-1 antibody screening and confirmatory testing. OraSure HIV Clinical Trials Group.

OBJECTIVE: To determine accuracy of a human immunodeficiency virus type 1 (HIV-1) antibody testing system using a device to collect and stabilize oral mucosal transudate (OMT), a fluid with increased levels of IgG; an enzyme immunoassay (EIA) screening test optimized for OMT; and a Western blot confirmatory test designed for use with OMT. DESIGN: The OMT specimens were tested by EIA and, if indicated, confirmatory Western blot according to a standard testing algorithm. The OMT results were compared with true HIV status as determined by serum testing and/or clinical diagnosis. PATIENTS: Specimens from 3570 subjects (2382 at low risk, 698 at high risk, 242 with acquired immunodeficiency syndrome [AIDS], and 248 "nonspecificity" [persons with diseases associated with an increased frequency of false-positive results in HIV testing]) were collected at 11 geographically diverse sites (including blood banks, public health clinics, general medical clinics, HIV clinics, sexually transmitted disease clinics, and a hemophilia center) in the United States. MAIN OUTCOME MEASURES: Overall accuracy of testing OMT for HIV-1 antibodies compared with true HIV-1 antibody status; sensitivity and specificity of OMT EIA and Western blot. RESULTS: Sensitivity of OMT EIA testing in 673 true-positive subjects was 99.9% (672/673). The OMT Western blot results in the 673 true-positive subjects were positive in 665 and indeterminate in 8. The EIA followed by Western blot (if EIA was repeatedly reactive) yielded a negative result in 99.9% (2893/2897) of OMT samples from true negatives and an indeterminate result in 4. The OMT testing system provided the correct result or would trigger appropriate follow-up testing in 3569 (>99.9%) of 3570 cases. CONCLUSION: HIV-1 antibody testing of OMT samples is a highly accurate alternative to serum testing.

Algorithms↗

Interaction between infrared radiation and vitreous substitutes.

OBJECTIVE: To characterize the interaction between midintrared radiation of cutting lasers used or proposed for vitreoretinal surgery and fluid vitreous substitutes commonly used in vitreoretinal surgery. METHODS: Optical transmittance of vitreous substitutes was measured with a double-beam spectrophotometer. Measurements were performed in a wide spectral range of infrared radiation, including the 2120-nm wavelength of the holmium-YAG laser and the water absorption peaks at 1440, 1930, and 2940 nm. RESULTS: The wavelengths considered have a penetration depth varying from 410 to 1 microns in Ringer's solution, balanced salt citrate-buffered solution, balanced salt bicarbonated-buffered solution, hyaluronate sodium, and hydroxypropyl methylcellulose ophthalmic solution, from 2000 to 13 mm in perfluorocarbon liquid, and from 52 to 2.5 mm in silicone and fluorosilicone oils. CONCLUSIONS: Midinfrared optical radiation exhibits dramatic differences of penetration depth in different vitreous substitutes. High-absorbing liquids should be used mainly with contact laser procedures and could provide a shield for remote structures. Low-absorption vitreous substitutes allow noncontact laser surgical procedures, but they also may cause direct optical damage to remote tissues. The knowledge of wavelength transmittance of vitreous substitutes is necessary to evaluate and optimize the efficacy and safety of cutting laser sources.

Fluorocarbons↗

Seroepidemiology of emerging tickborne infectious diseases in a Northern California community.

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51(23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11-20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.

Adolescent↗

Human immunodeficiency virus in plasma and genital secretions during the menstrual cycle.

Six human immunodeficiency virus (HIV)-positive women were studied weekly over 8 weeks to detect HIV RNA in plasma and cervical secretions and proviral DNA in cervical, vaginal, and cervicovaginal lavage samples by polymerase chain reaction (PCR) amplification techniques. In cervical swab samples, cell-free HIV RNA was detected more frequently than cell-associated HIV proviral DNA (22/48 vs. 7/48, respectively). Cervical HIV RNA was consistently detected in 2 women with plasma HIV RNA > 100,000 copies/mL but was not detected in 2 women with plasma HIV RNA < 10,000 copies/mL, regardless of menstruation status. HIV-specific IgA was detected in the plasma of 2 women and in at least 1 cervicovaginal lavage sample from all 6 women. Thus, quantitation of cervical HIV RNA can be accomplished by PCR techniques and may be useful in evaluation genital viral shedding.

Adult↗

Comparison of four enzyme immunoassays for detection of human T-cell lymphotropic virus type 2 antibodies.

Four licensed enzyme immunoassay (EIA) kits for the measurement of antibody to human T-cell lymphotropic virus (HTLV) type 1, one from Organon Teknika Corp. (OTC), one from Cambridge Biotech Corp. (CBC), and two from Abbott Laboratories (the 1993 modification [Abb 93] and the 2.0 version licensed in 1995 [Abb 95]), were evaluated for sensitivity and specificity in the detection of HTLV type 2 antibody, and the results were compared with those previously obtained with earlier kit versions. The CBC, Abb 95, Abb 93, and OTC kits had sensitivities of 99.7, 97.6, 96.8, and 96.2%, respectively, compared with sensitivities of 89.1 and 60% for the Abbott and CBC (previously DuPont) kits, respectively, licensed in 1988. Thus, the abilities of commercial kits to detect HTLV antibody have improved. The relative specificities of the CBC, Abb 95, Abb 93, and OTC kits with negative blood donor specimens that had been reactive with the 1988 CBC EIA kit were 92.9, 64.5, 78.8, and 62.6%, respectively. Compared with those of the 1988 versions, the specificity of the Abbott EIA has decreased and the specificity of the CBC kit has been significantly improved.

Blood Donors↗