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Biomedical subjects

B Reyes

Publications and source records attributed to B Reyes.

At least 19 recordsLinked to original sources

Cytotoxic proteins combined with prodigiosin obtained from Serratia marcescens have both broad and selective cytotoxic activity on tumor cells.

Cytotoxic proteins and prodigiosin obtained from Serratia marcescens strains are known to induce tumor cell death, nevertheless its combination has not been studied. In this paper we evaluate the combined effects of these molecules in a panel of tumor cell lines. The results showed a marked inhibitory effect on the growth of tumor cell lines derived from tumors (i.e., melanoma) which are highly resistant to conventional anticancer drugs, while normal cells were less sensitive than tumor cells. TUNEL (TdT-mediated dUTP nick end labeling) and electrophoresis of HEp-2 cell DNA treated with MG2327 preparation [containing the P50 protein belonging to the serralysins and prodigiosin, from S. marcescens CMIB4202] showed a pattern of DNA fragments typically associated with apoptosis. Interestingly, prodigiosin enhanced by 1.6-fold the cytotoxic effect of P50 when acting in combination on HEp-2 cells. The broad cytotoxic activity of the combination on tumor cells as well as its selectivity open new frontiers in cancer therapy.

Anti-Bacterial Agents↗

Chromatographic removal combined with heat, acid and chaotropic inactivation of four model viruses.

The virus removal of protein A affinity chromatography, inactivation capacity, acid pH and a combination of high temperature with a chaotropic agent was determined in this work. The model viruses studied were sendaivirus, human immunodeficency virus (HIV-IIIb), human poliovirus type-II, human herpesvirus I and canine parvovirus. The protein A affinity chromatography showed a maximum reduction factor of 8 logs in the case of viruses larger than 120 nm size, while for small viruses (18-30 nm) the maximum reduction factor was about 5 logs. Non viral inactivation was observed during the monoclonal antibody elution step. Low pH treatment showed a maximum inactivation factor of 7.1 logs for enveloped viruses. However, a weak inactivation factor (3.4 logs) was obtained for DNA nonenveloped viruses. The combination of high temperature with 3 M KSCN showed a high inactivation factor for all of the viruses studied. The total clearance factor was 23.1, 15.1, 13.6, 20.0 and 16.0 logs for sendaivirus, HIV-IIIb, human poliovirus type-II, human herpesvirus I and canine parvovirus, respectively.

Animals↗

Amoebicidal and giardicidal compounds from the leaves of Zanthoxylum liebmannianun.

The crude ethanol extract from the leaves of Zanthoxylum liebmannianum exhibited inhibitory effect on the reproduction of trophozoites of Entamoeba histolytica (IC(50)=3.48 microg/ml) and Giardia lamblia (IC(50)=58.00 microg/ml). From this extract, asarinin, hyperin, beta-sitosterol, and beta-sitosterol glucoside were isolated. Among them, asarinin was the most active with IC(50) values of 19.86 microg/ml for E. histolytica and 35.45 microg/ml for G. lamblia. The remaining compounds showed moderate activity against both parasites.

Amebicides↗

Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia.

The activity-guided fractionation of the ethanol extract of leaves of Annona diversifolia Saff., led to the isolation of palmitone (16-hentriacontanone) as the only anticonvulsant active compound. This aliphatic ketone was highly effective to diminish pentylenetetrazole (PTZ)-induced clonic-tonic seizures and toxicity. Also, it produced a prolongation of the latency for onset of seizures and a reduction of the death rate produced by 4-aminopyridine (4-AP) and bicuculline (BIC). However, it was inactive to inhibit the kainic acid (KA)- and strychnine (STC)-induced seizures. Palmitone did not produce motor incoordination and loss of righting reflex which are used as signs of neurological impairment. Palmitone (ED50 = 1.85 mg/kg) proved to be a more potent antiepileptic drug against the PTZ-induced seizures than etosuximide (ED50 = 59.6 mg/kg), sodium valproate (ED50 = 63 mg/kg), and carbamazepine (ED50 > 300 mg/kg) and it was only four-fold less potent than diazepam (ED50 = 0.48 mg/kg). The pharmacological profile of palmitone suggests that this compound could be acting on the GABAergic inhibitory system.

Animals↗

Allogeneic bone marrow transplantation versus chemotherapy for the treatment of childhood acute lymphoblastic leukemia in second remission: a single-institution study.

PURPOSE: A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively RESULTS: The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 x 10(9)/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 x 10(9)/L (DFS, 73% v35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%). CONCLUSION: In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.

Antineoplastic Agents↗

One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases. OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial. METHODS: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure. RESULTS: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle. CONCLUSION: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.

Administration, Topical↗

Comparison of long-term outcome of children with severe aplastic anemia treated with immunosuppression versus bone marrow transplantation.

Children with severe aplastic anemia (SAA) are treated with bone marrow transplantation (BMT) if a human leukocyte antigen (HLA) compatible sibling donor is available, or alternatively with immunosuppressive therapy (IST). Three retrospective trials examining BMT vs IST in pediatric patients treated from 1970-1988 found BMT resulted in a superior survival rate. Advances have been made in general supportive care and in the approach to each of these treatment modalities in the last decade. To compare survival following BMT and IST in a more recent era, we retrospectively analyzed the results of 48 consecutively treated children with SAA presenting to Memorial Sloan-Kettering Cancer Center (MSKCC) between 1983 and 1992. In contrast to the previous studies, the estimated survival of the BMT and IST groups at 120 months are equivalent, 75.6% and 73.8%, respectively. The IST results in our series are superior to the 42-48% (2-10 year) survival previously published, but similar to survival data observed in more recent IST trials employing more intensive immunosuppression (antithymocyte globulin and cyclosporine). The overall BMT survival rates are similar to those previously published, although BMT results improved dramatically during the latter five years of this analysis, with all 11 patients transplanted surviving with a minimum follow-up of 3 years. No surviving BMT patient has extensive chronic graft-versus-host disease (GvHD), a major cause of long-term mortality post-BMT. Therefore, it is likely the BMT survival curve will remain stable. In contrast, the survival curve of the IST patients is likely unstable, since patients are still at risk for relapse or development of clonal disease. Thus, despite overall similar survival rates, we continue to recommend BMT as first-line therapy in pediatric SAA patients with matched sibling donors.

Adolescent↗

Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis.

We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; chi 2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; chi 2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (chi 2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Anti-bombesin monoclonal antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures.

Fetal pulmonary neuroendocrine cells (PNECs) contain abundant gastrin-releasing peptide (GRP, mammalian bombesin-like peptide [BLP]). Previously, addition of bombesin resulted in increased fetal lung growth and maturation in utero and in organ cultures. A monoclonal antibody (mAb) to bombesin (2A11) blocked baseline automaturation of lung organ cultures in serum-free medium. In the present study, we analyze lung development following daily in utero administration of 2A11 from gestational days 15-18. Fetal lung treated with 2A11 and then harvested on day 18 demonstrated a dose-dependent decrease in surfactant phospholipid synthesis compared to controls treated with MOPC, an unreactive mAb. However, 2A11-treated fetal lung harvested on day 17 showed paradoxical increases in 3H-choline incorporation into saturated phosphatidylcholine, 3H-thymidine incorporation into DNA, and relative numbers of differentiated type II pneumocytes. In serum-containing day 17 lung organ cultures, 2A11 stimulated choline and thymidine incorporation. Since epidermal growth factor (EGF) is the only agent besides bombesin known to stimulate both fetal lung growth and maturation, we added EGF to serum-free cultures and reconstituted the stimulatory effects. A murine EGF receptor mAb (ERA) blocked 2A11-induced lung growth and maturation in serum-containing cultures, and this effect was overcome by adding EGF. In vivo, ERA also blocked stimulatory effects of 2A11 in fetal lung on day 17. These observations suggest that EGF receptor up-regulation may maintain lung growth and maturation if BLP levels are diminished on day 17. Nonetheless, BLPs appear to be involved in lung maturation on day 18, supporting a role for PNECs in normal lung development.

Animals↗

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Cell Differentiation↗

The role of motile aeromonads in the fish disease, ulcerative disease syndrome (UDS).

Ulcerative Disease Syndrome (UDS) is an epizootic fish disease characterized by the presence of severe, open dermal ulcers on the head, midbody, and dorsal regions of the fish. Aeromonas hydrophila and A. sobria were recovered more often from UDS fish than other bacteria from the genera Vibrio, Alteromonas and Plesiomonas. Representative isolates of A. hydrophila, A. sobria, V. anguillarum, V. vulnificus, Alteromonas putrefaciens, and P. shigelloides taken from UDS and healthy fish were assayed for virulence-associated factors. The aeromonads produced a wide variety of hydrolytic enzymes and expressed cell surface characteristics linked to virulence whereas the other bacterial species rarely produced the same enzymes or cell surface characteristics. The role of aeromonads in UDS is believed to be opportunistic or secondary and these bacteria are thought to play an important role in this degenerative disease.

Aeromonas↗

Acquired progressive lymphangioma.

Acquired progressive lymphangioma is rare and can histologically mimic well-differentiated angioendothelioma. In a 9-year-old boy with acquired progressive lymphangioma, we demonstrated that the neoplasm consists of at least a vascular component and a smooth muscle component. The presence of type IV collagen around many vascular channels suggests that an intermediate stage of differentiation between blood vessels and lymphatics may be present. Our findings indicate that acquired progressive lymphangioma is most likely a complex hamartoma composed of vascular channels and smooth muscle.

Basement Membrane↗

Signal-detection analysis of recognition memory of obese subjects.

Obese and normal-weight subjects were run on a series of recognition-memory tasks with low and high meaningful CVC trigrams. Subjects received feedback or no feedback regarding the appropriateness of their answers during testing for recognition memory. A signal-detection analysis was used to examine a relatively pure index of memory (d') as compared to response-bias factors [Ln (beta)]. No significant main effect on memory of obese and control subjects was noted although a significant interaction indicated that obese subjects' memory increases over trials in a differential fashion from normal-weight individuals with poorer performance among the obese after 3 trials. Feedback facilitated memory for both groups. Analysis of response criteria [Ln (beta)] showed no significant difference between groups. Highly meaningful trigrams had a significantly lower response criterion than low meaningful trigrams and there was a significant interaction of meaningfulness by trials. An interaction of feedback by meaningfulness was also present. Advantages of using a signal-detection analysis in memory studies comparing obese and normal weight subjects are discussed. Ramifications of the present data for the internality/externality hypothesis of obesity are also discussed.

Adolescent↗

Sensory and non-sensory factors and the concept of externality in obese subjects.

9 obese and 9 normal subjects performed a psychophysical task in which food- or non-food-related stimuli were briefly flashed tachistoscopically at a speed and intensity near the visual threshold. A signal was presented on one-half the trials and noise only on the other one-half of the trials. Using signal detection theory methodology, separate measures of sensory sensitivity (d') and response bias (beta) were calculated. No differences were noted between obese and normal subjects on measures of sensory sensitivity but significant differences on response bias. Obese subjects had consistently lower response criteria than normal ones. Analysis for subjects categorized by whether they were restrained or unrestrained eaters gave findings identical to those for obese and normal. The importance of using a methodology that separates sensory and non-sensory factors in research on obesity is discussed.

Adult↗

Sensitivity to proprioceptive feedback in obese subjects.

40 subjects, 20 obese and 20 normal, were run on a weight-discrimination task requiring judgments dependent on proprioceptive feedback. A signal-detection analysis was used to separate sensory factors from non-sensory, response-bias factors in the analysis of the discriminations. Obese subjects were inferior to normals in ability to make sensory discriminations; the largest differences occurred between obese and normal males. Obese subjects also adopted a more strict criterion (beta); the largest differences again occurred for male subjects. Obese subjects showed more variability in their sensory judgments, although there was a significant difference on only one of the 5 discrimination tasks. Results are discussed in terms of the internal-external explanation of obesity.

Adult↗