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Biomedical subjects

L Mendoza

Publications and source records attributed to L Mendoza.

At least 19 recordsLinked to original sources

[High-dosage chemotherapy and the autologous transplantation of peripheral hematopoietic progenitor cells in breast cancer: the initial results, analysis of toxicity and the necessary support means].

BACKGROUND: In the last years high dose chemotherapy (HDC) schedules have been developed with autologous bone marrow transplantation (ABMT) which are very effective in breast cancer. Expectation has been raised concerning the cure of a subgroup of patients with metastatic breast cancer and the improvement of prognosis in high risk stages II and III. METHODS: CTCb (cyclophosphamide 6 g/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2) was administered with autologous peripheral hematopoietic progenitor cells transplantation (TACPHP) and granulocytic colony stimulating factor (G-CSF) 5 micrograms/kg/day to 27 patients with breast cancer: 9 in stage IV in complete remission, 12 in stage II with > or = 10 affected lymph nodes and 6 in stage III. RESULTS: No toxic deaths were reported. The median time to achieve > or = 0.5 x 10(9) neutrophils/l was 8 days, to > or = 20 x 10(9) platelets/l 9 days and to > or = 50 x 10(9) platelets/l 12 days. Fever was observed in 85% of the patients although its median duration was of only one day. Extrahematologic toxicity was moderate with grade III nausea/vomiting in 48% of patients, grade III mucositis in 22%, grade III hepatitis in 19%, and grade III diarrhea in 4%. No grade IV toxicity was observed. The median follow-up is still short (10 months, range: 2-25). All the patients maintain normal hematologic peripheral blood counts and only 4 (in stage IV) have relapsed. CONCLUSIONS: The slight extrahematologic toxicity observed in the high dose chemotherapy with cyclophosphamide, thiotepa and carboplatin, and the rapid hematologic recovery provided by the TACPHP and G-CSF allow the above schedule to be administered with moderate toxicity and no mortality. This low toxic profile leads to the possibility of future trials with this chemotherapy schedule in other subgroups of patients with breast cancer.

Adult

Use of the polymerase chain reaction to identify coding sequences for chitin synthase isozymes in Phialophora verrucosa.

Based on conserved amino-acid regions predicted for the chitin synthases (Chs) of Saccharomyces cerevisiae, two different primer sets were synthesized and used in polymerase chain reactions (PCRs) to amplify 614-bp and 366-bp sequences from genomic DNA of the zoopathogenic fungus Phialophora verrucosa. DNA-sequencing and Southern-blotting analyses of the 614-bp DNA amplification products suggested that portions of two distinct P. verrucosa chitin synthase genes (PvCHS1, PvCHS2), coding for two different zymogenic-type PvChs isozymes, had been identified. The deduced amino-acid sequence of each fell into different Chs classes, namely class I and class II. In addition, the 366-bp DNA segment was shown to code for a conserved region having homology with the CSD2/CAL1 gene of S. cerevisiae, which encodes a nonzymogenic-type enzyme, Chs3, in that fungus. The amino-acid sequence derived from PvCHS3 exhibits 88.2% similarity and 78.4% identity to the same amino-acid region of the S. cerevisiae enzyme. These results provide a critical first step toward investigating the molecular and pathogenic importance of CHS gene regulation in this fungus and for exploring steps leading to Chs function as potential targets for the design of new therapeutic agents.

Amino Acid Sequence

Modulation detection interference using random and sinusoidal amplitude modulation.

The detection of amplitude modulation (AM) of a target sound is made more difficult by the presence of a modulated sound some spectral distance from the target. This effect (modulation detection interference, or MDI) was examined for stimuli with random amplitude modulations (RAM) and for sounds with sinusoidal amplitude modulations (SAM) as a function of average modulation depth (m) of the interferer. In an experiment comparing comodulated and independent RAM targets and interferers, the amount of interference was not related to the modulation coherence of the target and interferer. Elevations in AM threshold increased as a function of m in a similar way for both conditions. The MDI for RAM and SAM targets and interferers was also compared. While no difference was found for AM detection of RAM and SAM, MDI was found to be greater for the RAM stimuli than for the SAM stimuli. A subsidiary experiment comparing RAM and SAM modulation depth discrimination indicated that RAM discrimination is more difficult than SAM discrimination. Taken together, these results are quantitatively consistent with a mechanism resembling AM discrimination as the underpinning of MDI in conditions where the target and interferer are synchronously gated.

Adult

Perceptual organization in a comodulation masking release interference paradigm: exploring the role of amplitude modulation, frequency modulation, and harmonicity.

Two areas of interest within auditory scene analysis are the identification of cues which contribute to auditory grouping and/or segregation, and the methodology employed to measure such effects. The present study explored the roles of three purported grouping cues--correlated AM, correlated FM, and harmonicity--using a comodulation masking release interference paradigm. This method was reasoned to be free of alterations in the subject's mode of listening (analytic versus synthetic). The results suggested that correlated AM was a viable grouping cue. For some listeners, the presence of FM also appeared to provide a grouping cue, but, generally, no effect of coherence of FM was observed. No effect of harmonicity was observed in this paradigm.

Adult

Within- and across-channel processes in modulation detection interference.

Modulation detection interference (MDI) describes the effect of an amplitude-modulated sound on detection of amplitude modulation (AM) on a spectrally distant target sound. In MDI, AM detection is worsened by an AM interfering sound. Previous research has implicated both within-channel and across-channel processes as the basis for MDI. This study examined the detection of 10-Hz sinusoidal AM as a function of the spectral relationship, gating synchrony, and ear of presentation of the target and interfering sounds. Using a 993-Hz target sound, AM detection improved as the frequency of the interferer increased from 1250 to 2188 Hz, and as it decreased from 788 to 450 Hz. MDI was less for continuous interferers than for interferers gated synchronously with the target. In the continuous interferer conditions, however, MDI was still greatest for interferers most proximal to the target. The effects of frequency proximity and gating asynchrony were also evident using interferers presented to the ear contralateral to the target ear. While a 1250-Hz interferer led to more MDI than a 788-Hz interferer when the interferers were presented to the same ear as a 993-Hz target, no significant asymmetry was noted with dichotic stimulation. Taken together, the results of these experiments indicated that MDI is the result of across-channel, and to a limited extent, within-channel processes.

Adult

Control of myocardial reperfusion injury with hypertonic-hyperosmotic solution in isolated rabbit heart.

The effects of postischemic reperfusion were investigated in 14 isolated rabbit hearts in Langendorff preparation. Seven were controls and the others were reperfused with a sodium 7.5% and dextran 60 (60,000 MW) solution diluted with Krebs-Henseleit buffer to a sodium concentration of 150 mEq/l. The incidence of arrhythmias was lower in this group (p = 0.034). Coronary flow was higher than in controls (p = 0.035), the levels of isoenzyme MB of creatine kinase were lower than in controls (p = 0.035), myocardial water content was also lower (p = 0.047), and histological damage was reduced (p = 0.018). It was concluded that early reperfusion with 7.5% sodium chloride, 6% dextran 60 solution has a protective effect in the treatment of cardiac reperfusion injury.

Animals

[Intensive chemotherapy with support of peripheral hematopoietic progenitor cells, mobilized with high-dose cyclophosphamide and G-CSF: fast hematologic recovery].

BACKGROUND: Hematopoietic progenitor cells mobilized to peripheral blood by a chemotherapy combined or not with hematopoietic growth factors and harvested with cyto-apheresis (CTA) provide a rapid hematological recovery when infused as a support step after intensive chemotherapy (IC). METHODS: Cyclophosphamide (CI) 4 g/m2 and G-CSF 5 mcg/kg/d were administered to 19 patients with a solid tumor or lymphoma. Daily CTA were performed during hematological recovery to harvest > 2.5 x 10(6) cells CD34+/kg. Seventeen patients received IC with infusion of peripheral hematopoietic progenitor cells (PHPC) and G-CSF. RESULTS: A total of 52 CTA were performed, with a median (M) of 2 per patient. A M of 4.4 x 10(8) mononucleated cells/kg and 9.8 x 10(6) CD34+/kg were harvested per patient. Hematological recovery after IC with support of PHPC and G-CSF was rapid in all cases, but the aplastic period was shorter in the ten patients who received > 5 x 10(6) CD34+/kg cells than in the seven patients with < 5 x 10(6) kg: The median of recovery to neutrophils > 0.5 x 10(9)/l was 8 days compared with 9 days (p = 0.0005), to platelets > 20 x 10(9)/l of 8 days compared with 12 days (p = 0.001), and to platelets > 50 x 10(9)/l of 11 days compared with 14 days (p = 0.001). CONCLUSIONS: Toxicity of IC (4 g/m2) with G-CSF is moderate and allows the harvesting of an adequate number of PHPC. Its infusion after IC provides a rapid hematological recovery, which was more marked in patients receiving 5 x 10(6) CD34+/kg cells, than with the same IC schedules of IC with autologous bone marrow transplantation.

Adult

[Dermatomyositis and head and neck neoplasia].

The incidence of malignant disease appears to be increased in patients with dermatomyositis, although the relationship between dermatomyositis and cancer is still controversial. The most frequently associated tumors are not different from the tumors observed in the general population. There are very few cases of head and neck cancer associated with myositis reported in the medical literature despite the high incidence of these tumors in western countries. Two new cases are reported and the relationship between myositis and cancer is discussed.

Adult

Identification of three chitin synthase genes in the dimorphic fungal pathogen Sporothrix schenckii.

Degenerate PCR primers were used to amplify a 600-bp conserved gene region for chitin synthases from genomic DNA of Sporothrix schenckii, a dimorphic fungal pathogen of humans and animals. Three chitin synthase gene homologs were amplified as shown by DNA sequence analysis and by Southern blotting experiments. Based on differences among the predicted amino acid sequences of these homologs, each was placed within one of three different chitin synthase classes. Phylogenies constructed with the sequences and the PAUP 3.1.1 program showed that S. schenckii consistently clustered most closely with Neurospora crassa in each of the three chitin synthase classes. These findings are significant because the phylogenies support by a new method the grouping of the imperfect fungus S. schenckii with the Pyrenomycetes of the Ascomycota.

Base Sequence

[High-dose chemotherapy and autologous bone marrow transplantation in high-grade metastatic sarcomas].

Metastatic sarcomas have a poor prognosis with current therapeutic regimens. High dose chemotherapy (HDC) has proved to be efficient in a selected group of solid tumors. Nine patients with high grade metastatic sarcomas were treated with HDC followed by autologous bone marrow transplantation. Four patients received HDC as a consolidation of the complete response (CR) obtained with chemotherapy (CT) and two of them were free from disease at 27 and 41 months, respectively. Other four patients had a disease total or partially refractory to conventional CT, and in one case the sensitivity to the chemotherapeutical agents was unknown. In these five cases a partial response was observed in two of the three who had measurable response parameters, but all of them died because of disease progression in a short period of time. These results suggest that there are active HDC schedules on metastatic sarcomas, but its possible benefit would be limited to the consolidation of a CR obtained with previous CT. HDC is a therapeutical alternative under investigation in patients with metastatic sarcomas with an indication that could be extended to cover localized sarcomas with poor prognosis.

Adolescent

Life cycle of the human and animal oomycete pathogen Pythium insidiosum.

Pythium insidiosum, the etiologic agent of pythiosis insidiosii, causes life-threatening infections in humans and animals. Previous studies of the epidemiology of this disease hypothesized about the possible life cycle of this oomycete. Details, however, were not provided on the steps required to cause infection. We investigated the life cycle of P. insidiosum by inoculating pieces of equine skin and plant leaves and then studying the ensuing events with a scanning electron microscope. Our observations revealed that zoospores had a strong tropism for skin tissue, horse and human hair, and water lily and grass leaves and a weak attraction to a variety of other leaves. Encysted zoospores were observed on the favored leaves and skin. There they produced germ tubes and later abundant hyphal filaments that penetrated leaf tissues. Young sporangia had compact, thick walls. The sporangial wall was reduced to a fragile membrane when the sporangia had produced well-differentiated biflagellate zoospores. The encysted zoospores secreted an amorphous material that permitted the zoospores to adhere to skin and plant tissues. On the basis of these findings, a model to explain the life cycle of P. insidiosum is proposed.

Animals

Cell cycle regulation of polymorphism in Wangiella dermatitidis.

Phenotypic switching in Wangiella dermatitidis between polarized growth processes leading to yeast budding or hyphal apical extension and nonpolarized processes leading to isotropically enlarged forms that may become multicellular is a cell-cycle related phenomenon. Exit of yeasts from the budding growth cycle by this polymorphic agent of phaeohyphomycosis can be induced by incubation of wild-type (wt) cells in pH 2.5 medium at 25 degrees C, or of certain temperature-sensitive, cell-division-cycle (cdc) mutants at pH 6.5 at 37 degrees C. Continued incubation under these semirestrictive conditions causes yeasts to form unbudded, multinucleate, multicellular phenotypes that resemble the sclerotic bodies of chromoblastomycotic fungi. However, new results with Ca2+ indicate that at pH 2.5 critical, but low, concentrations of this ion are crucial for regulating multicellular form development, higher concentrations allow maintenance of polarized growth, and that switching between polarized and nonpolarized growth may involve a Ca2+/proton exchange mechanism. Support for this important role for Ca2+ is provided by experiments with EGTA in media buffered against pH change at near neutrality. Under these conditions, withholding Ca2+ with high EGTA concentrations caused yeasts to arrest in a terminal phenotype characterized by the presence of a bud initial that tended not to enlarge. In contrast, lower concentrations of EGTA often induced yeast-to-multicellular-form conversion. Other new results have suggested that even brief culture of yeasts under conditions that arrest their budding growth cycles may induce commitment to phenotypic transitions.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium

Evaluation of two vaccines for the treatment of pythiosis insidiosi in horses.

Two vaccines to treat phythiosis insidiosi in horses were evaluated in 71 Costa Rican horses between 1982 to 1988. One vaccine used a cell-mass (CMV) as antigen and the other a soluble concentrated antigen (SCAV). Both vaccines cured horses infected with Pythium insidiosum (p value approximately 14%). The age of lesions prior to vaccination was important in the response of the horses to immunotherapy. All horses with lesions 0.5 months or less in duration were cured regardless of the vaccine used. Horses with lesions two or more months old did not respond to either vaccine. The age of the horses did not have any influence on their response to the vaccinations. The CMV produced a prominent inflammatory reaction at the side of injection, while the SCAV gave a low inflammatory reaction. In addition, the CMV lost its effectiveness two to three weeks after its preparation. By contrast, the SCAV maintained its ability to cure horses even after 18 months. Immunotherapy using SCAV can thus be used as the vaccine of choice in early cases of equine cutaneous pythiosis insidiosi.

Aging

Serodiagnosis of leptospirosis in pigs using an axial filament enzyme-linked immunosorbent assay.

The axial filament (AF) from Leptospira interrogans serovar canicola was isolated by cesium chloride density gradient centrifugation of 2% sarcosyl treated whole cells. Isolation of AF was confirmed by electron microscopic examination, by protein-A immunogold labelling, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and immunoblotting. Analysis by SDS-PAGE of the purified preparation showed relatively weak bands of molecular size 41 kDa and 21 kDa, and strong bands of 35 kDa and 34.5 kDa. Immunoblot analysis using antiserum to the AF against sonicated leptospires of a variety of serovars showed prominent reaction against the 41, 35, and 34.5 kDa protein bands, as well as against minor bands of molecular weight 43, 39, and 37 kDa. Antisera prepared against leptospiral serovars also identified minor bands at 33 and 32 kDa. Immunoblots with antiserum to whole cells of serovar bratislava detected the 35 and 34.5 kDa AF bands of Borrelia burgdorferi moderately and of Treponema hyodysenteriae only slightly in comparison to leptospiral AF. Antibody to B. burgdorferi did not detect the leptospiral AF antigen. Immunoblots with antiserum to T. hyodysenteriae showed a marked reaction with a 41 kDa band of B. burgdorferi but only a very minor reaction with leptospiral AF. The AF was tested in an AF-ELISA against sera from 260 pigs, many of which reacted in the microscopic agglutination test (MAT) against one or more leptospiral serovars. A sensitivity of 97.1% and a specificity of 93.1% was determined in comparison to the MAT. Only moderate correlation was observed between titres detected in the AF-ELISA and the MAT (r = 0.4). When sonicated whole cells (WC) of serovar canicola were used in an ELISA (WC-ELISA), high correlation was observed between AF-ELISA and WC-ELISA (r = 0.97). These findings show that the AF-ELISA can be used effectively as a species-specific antigen for the serological diagnosis of leptospirosis in swine and that sonicated whole cells can substitute excellently for purified AF as the antigen source. These findings may be extrapolated to the use of AF in immunodiagnosis of leptospirosis in other species.

Agglutination Tests

Immunoblot analysis of the humoral immune response to Pythium insidiosum in horses with pythiosis.

Reactions to Pythium insidiosum by sera from horses with active pythiosis were investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Five strains of P. insidiosum were grown in nutrient broth and then sonicated. After centrifugation, supernatant antigens were separated by SDS-PAGE. An exoantigen of Conidiobolus coronatus was also tested. Bands with molecular weights between 97,000 and 14,000 were identified by Coomassie blue and silver staining. After being transferred to nitrocellulose, the antigens were reacted against sera from six horses with pythiosis, sera from four horses cured a year earlier by vaccination, and sera from five healthy horses. The sera from horses with pythiosis recognized at least 20 antigens in all strains. Three antigens with molecular weights of 32,000, 30,000, and 28,000 appeared to be immunodominant and specific. Sera from horses cured by immunotherapy showed only five very weak bands, three of them the 32,000-molecular-weight (32K), 30K, and 28K antigens. No bands were observed with sera from healthy horses or sera from horses with a variety of other infections. Sera from horses with pythiosis cross-reacted with the 44K antigen of C. coronatus. The immunodominant antigens described here may be useful for diagnostic purposes and in immunotherapy for this oomycotic infection in horses.

Animals

[Nephrotic syndrome in children. Retrospective study at a concentration hospital].

In order to evaluate the usefulness of certain clinical and paraclinical characteristics to be able to discriminate the minimal change disease (MCD) from other histopathological lesions associated with the nephrotic syndrome (NS), the clinical charts of 31 patients were reviewed and relevant data were analyzed. Those patients with no history of biopsy and those with documented MCD through biopsy, were placed in one group (MCD = 25) and the rest as others (others = 6). None of the clinical or paraclinical indicators analyzed showed significant differences between either group. In the MCD group, 76% of the patients entered remission after receiving steroid treatment, while none of the others entered remission. The magnitude of the proteinuria, hypoalbuminemia, hypercholesterolemia, and the presence of hematuria, hypertension or hyperazoemia, were not useful to discriminate those with MCD from other lesions. The response to treatment with prednisone was the most useful data to differentiate the groups.

Child