Contact dermatitis due to levobunolol in eyedrops.
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Administration, Topical↗
Biomedical subjects
R Perez
Publications and source records attributed to R Perez.
Genetic variability and geographic differentiation among three species of Triatomine bugs (Hemiptera-Reduviidae).
Three species of triatomine bugs, Triatoma sordida, T. guasayana, and T. patagonica, were examined by cytogenetic (C-banded karyotypes and male meiotic process) and isoenzymatic studies. These three species, with different importance as Chagas' disease vectors, were found to be closely related according to their known ethologic, ecologic, and morphologic traits. Although they have the same diploid chromosome number (2n = 22 constituted by 20 autosomes and an XY male/XX female sex mechanism), each species has a distinct chromosomal behavior during male meiosis and a specific amount and localization of C-heterochromatic blocks. Moreover, these chromosome characteristics allowed us to differentiate two T. sordida populations. Isoenzymatic data confirmed the taxonomic status of the three species and together with our cytogenetic results questioned the species homogeneity of T. sordida.
Animals↗
Translational studies of glutathione in bladder cancer cell lines and human specimens.
Glutathione (GSH) levels were measured in 13 human tumor cell lines derived from carcinomas of the bladder, ovary, and colon and from melanoma and glioblastoma. High levels were found in four of five bladder cell lines. The average GSH concentration in the bladder cell lines was approximately 6-fold higher than in the non-bladder cell lines. Because this difference suggested the possibility of elevation of GSH in urothelial neoplasia, we measured GSH in bladder tumor tissue from patients with transitional cell carcinoma (TCC) of the bladder (Group I, n = 17). GSH was also measured in two types of control tissues: (a) nontumor bladder tissue from patients with TCC or a history of TCC of the bladder (Group II, n = 23); and (b) bladder tissue from patients without bladder cancer (Group III, n = 14). Thirteen sets of paired specimens of tumor and nontumor bladder tissue from the same patient were evaluated. The tissues were flash-frozen, and GSH was measured after histological assessment of the same samples. Free and total GSH (free + mixed disulfides) were measured by a high-performance liquid chromatography assay with fluorescence detection and expressed as nanomoles/mg protein. The mean free GSH (+/- SD) for groups I, II, and III was 32.0 +/-18.7, 17.3 +/- 11.4, and 9.3 +/- 4.0, respectively, and the mean total GSH was 45.9 +/- 32.5, 23.7 +/- 17.1, and 12.2 +/- 6.7. The respective differences between groups (I and II, I and III, and II and III) were statistically significant for both free and total GSH (Ps ranging from <0.0001 to </=0.05). Free and total GSH were higher in tumor than in nontumor tissue in 11 of 13 paired specimens (free, 29.5 +/- 20.4 versus 18.7 +/- 11.7, P = 0.017; total, 41.7 +/- 33.8 versus 24.9 +/- 18.4, P = 0.005). No correlation was found between GSH levels and the proportion of tumor cells in the tissue. Influence of smoking on GSH expression could not be assessed because 81% of the patients with TCC had a smoking history. Similarly, because only 11% had prior cytotoxic chemotherapy, the influence of prior cytotoxic exposure on GSH could not be assessed. The results indicate: (a) significantly higher levels of GSH in TCC compared to tumor-free bladder tissue; and (b) higher GSH levels in nontumor bladder tissue from patients with bladder cancer than from patients without TCC. The clinical implications of this work include the possibility that GSH may play a role in the resistance of bladder cancer to chemotherapy and may be associated with bladder carcinogenesis.
Brain Neoplasms↗
Gangliosides expressed in human breast cancer.
Breast tumors that were histopathologically diagnosed as invasive ductal carcinoma were examined in relation to their abnormal expression of gangliosides. Total ganglioside levels that were expressed as lipid-bound sialic acids were significantly higher in breast tumor tissues than in normal mammary tissues. Two kinds of unusual gangliosides were found to be expressed in many cases of breast tumors. One was a group of O-acetylated gangliosides, such as O-acetyl-GD3 and O-acetyl-GT3. They are known as fetal gangliosides, which appear in fetal brains. The other was an N-glycolylneuraminic acid-containing ganglioside, N-glycolyl-GM3, which had not been previously found in normal human tissues. The finding that unusual gangliosides are expressed in breast tumors may provide the basis for their immunological diagnosis and vaccine therapy.
Breast Neoplasms↗
Altered glutathione metabolism in oxaliplatin resistant ovarian carcinoma cells.
Elevation of glutathione (GSH) is commonly observed in cellular resistance to a number of anticancer agents. Most frequently reported change in GSH metabolism that is associated with the elevated GSH levels is increased mRNA expression and activity of gamma-glutamyl cysteine synthetase (gamma GCS), the first enzyme of the GSH biosynthetic pathway. We have isolated sublines of the A2780 ovarian carcinoma cell line (C10 and C25) that are 8- and 12-fold resistant to oxaliplatin by repeatedly exposing the cells to increasing concentrations of the platinum agent. The GSH levels in C10 and C25 cell sublines are 3.1- and 3.8-fold higher than the parent A2780 cell line. The mRNA levels and activities for gamma GCS and that for gamma-glutamyl transpeptidase (gamma GT), the GSH salvage pathway enzyme, were measured in these cells. The mRNA for gamma GT and gamma GCS were measured by RT-PCR, with quantitation of the PCR product by HPLC; mRNA levels are expressed as ratios to beta-actin mRNA, used as an endogenous standard. GSH and gamma GCS activity were measured by HPLC assays and gamma GT activity by a colorimetric assay. The increase in GSH in C10 and C25 was associated with an elevation in gamma GT mRNA (2.5- and 8-fold) and gamma GT activity (2.7- and 2.8-fold). No changes were observed in gamma GCS mRNA levels or activity. The data indicate that alterations in GSH metabolism leading to elevations in cellular GSH in A2780 ovarian carcinoma cells selected for low levels of resistance to oxaliplatin are mediated by gamma GT, the "salvage' pathway, rather than an increase in GSH biosynthesis.
Antineoplastic Agents↗
Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: a comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure.
Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and prostaglandins (PGE2) have been reported in humans as early as 3 hr and as late as 18 hr after exposure. The purpose of this study was to determine whether a broad range of inflammatory mediators are elevated in BAl fluid within 1 hr of exposure. We exposed eight healthy volunteers twice: once to 0.4 ppm ozone and once to filtered air. Each exposure lasted for 2 hr during which the subjects underwent intermittent heavy exercise (66 liters/min). BAL was performed 1 hr after the exposure. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE2, thromboxane B2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the recovery of total cells and alveolar macrophages, and decreased ability of alveolar macrophages to phagocytize Candida albicans. A comparison of these changes with changes observed in an earlier study in which subjects underwent BAL 18 hr after an identical exposure regimen indicates that IL-6 and PGE2 levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a were present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time.
Adolescent↗
Increase in the lumen of the femoral artery in dogs with an arteriotomy encircled by glutaraldehyde-tanned calf pericardium.
A fast and simple experimental method of arterioplasty that produces enduring enlargement of the lumen of large arteries is described. We studied the long-term intraluminal patency of femoral arteries of four dogs subjected to a procedure in which a longitudinal 3-cm loophole was made in the artery and left open inside a girdling cylinder of glutaraldehyde-tanned calf pericardium. One year later, Doppler ultrasound and histological studies were performed in the operated and contralateral arteries. Lasting enlargement of the lumen was obtained along the 3-cm arteriotomy. The mean cross-sectional internal diameter in the middle of the surgical area was 2.2 +/- 0.1 mm, in contrast to 1.2 +/- 0.2 mm in the non-operated contralateral artery (P < 0.01). The ultrasound study showed an increase in blood flow and histological analysis demonstrated a threefold increase in the internal area of the arterial lumen, and new endothelium, which fully covered the operated segment. Our results showed an enduring increase in the lumen in segments of large arteries subjected to our new arterioplasty procedure.
Angioplasty↗
A comparative study of laparoscopy and colpotomy for the removal of ovarian dermoid cysts.
OBJECTIVE: To compare laparoscope-assisted transvaginal removal of dermoid cysts to more standard laparoscopic cystectomy techniques. METHODS: We conducted a retrospective review of 44 laparoscopic dermoid removals performed at Olive View-UCLA Medical Center between 1992 and 1995. Cases were divided into three groups based on surgical approach: 1) conventional laparoscopic ovarian cystectomy, 2) laparoscopic ovarian cystectomy and removal of the freed mass via colpotomy, and 3) laparoscopic inspection, then transvaginal cystectomy via colpotomy. Surgical time, estimated blood loss, cyst spillage, and complications were compared. RESULTS: There were 11-19 patients in each group. The groups were similar in patient age, parity, and weight. Larger cysts tended to be removed by the laparoscopy-colpotomy techniques (mean diameter 10 cm) rather than by the purely laparoscopic approach (mean diameter 7 cm, P < .05). Cyst spillage occurred less often (43%, P < .05) and surgical time was shortest (mean 81 minutes, P < .05) with laparoscope-assisted transvaginal ovarian cystectomy compared with conventional laparoscopic techniques. Disposable laparoscopic instruments were used less often with transvaginal cystectomy (7%) than with conventional laparoscopic cystectomy (77%, P < .01). The difference in mean estimated blood loss in the cases using colpotomy (89 mL) compared with cases that did not (65 mL) was not statistically significant. Among the three groups, there were four major operative complications related to blood loss and infection. CONCLUSION: Laparoscope-assisted transvaginal ovarian cystectomy allows the removal of larger dermoid cysts, with less cyst spillage and savings in operative time and equipment compared with conventional laparoscopic cystectomy.
Adult↗
Bone bacillary angiomatosis in an HIV-infected patient.
Bacillary angiomatosis (BA) is a recently discovered multisystem bacterial infectious disease seen in the setting of immune suppression due to the human immunodeficiency virus (HIV). A case of an HIV-infected patient with osteolytic bone involvement is reported.
Adult↗
Receptive field asymmetries and sensitivity to random dot stereograms.
The differences between the two monocular receptive fields of cortical cells were measured and compared to their disparity tuning in the awake behaving monkey. Several receptive field properties (direction selectivity, orientation preference, eye preference and response modulation) were determined for each eye using sweeping bright bars. The disparity sensitivity of these cells was also assessed by plotting their response profile, determined for each cell under strictly binocular cyclopean stimulation (dynamic random dot stereograms, RDS). We have found that large differences between the two monocular receptive fields were infrequent and, apparently, not related with the disparity sensitivity profile. We conclude that the monocular asymmetries tested in this study and the sensitivity to positional binocular disparities present in RDS, might be linked to different mechanisms involved in depth perception in the visual system.
Animals↗
Induction of gamma-glutamyl transpeptidase mRNA by platinum complexes in a human ovarian carcinoma cell line.
Elevation of glutathione (GSH) is widely observed in cellular resistance to platinum agents. Our previous studies have shown that sublines of human ovarian carcinoma cell line A2780, which exhibited low levels of resistance to oxaliplatin, showed elevated steady state levels of mRNA and activity of gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2), but not of gamma-glutamylcysteine synthetase (gamma-GCS, EC 6.3.2.2) [El-akawi et al., Cancer Lett. 105:5-14; 1966]. To understand this phenomenon better, we have studied the effect of single exposures of oxaliplatin or cisplatin on the mRNA expression of gamma-GT and gamma-GCS in A2780 cells. The mRNAs of gamma-GT and gamma-GCS were measured by reverse transcriptase PCR, with quantitation of the PCR product by HPLC; mRNA levels are expressed as ratios to beta-actin mRNA, used as an endogenous standard. GSH was measured by HPLC. The gamma-GT activity was measured by a colorimetric assay. Single exposures of cells to oxaliplatin induced a time- and concentration-dependent increase in the mRNA of gamma-GT, but not of gamma-GCS. Cisplatin also induced an elevation in gamma-GT mRNA, but to a lower degree. The gamma-GT enzyme activity increased corresponding to the elevation in mRNA expression. The gamma-GT-induced cells showed an increase in cellular GSH when incubated in medium containing GSH. The data suggest that a) single, brief exposures to pharmacologically relevant concentrations of platinum complexes induce elevation in mRNA of gamma-GT, b) elevation in gamma-GT mRNA translates into elevated gamma-GT activity and increase in GSH salvage, and c) the degree of induction of gamma-GT mRNA differs between platinum complexes.
Antineoplastic Agents↗
Cytotoxicity, cellular accumulation and DNA binding of oxaliplatin isomers.
Oxaliplatin (trans-l-1,2-diaminocyclohexane oxalato Pt(II); 1R,2R-dach, l-OHP), its trans-d isomer (1S,2S-dach) and cis-dach (1R,2S-dach) isomers were compared in in vitro testing against human ovarian carcinoma cell lines A2780, A2780/CP (cisplatin resistant), A2780/l-OHP (oxaliplatin resistant), colon carcinoma cell line HT-29, and murine leukemia cell lines L1210, L1210/CP (cisplatin resistant), and L1210/dach (tetraplatin resistant). The relative molar potency of the three complexes in all the cell lines except A2780/l-OHP and L1210/dach are trans-l > trans-d > cis-dach; in A2780/l-OHP they are trans-l = trans-d > cis-dach; in L1210/dach trans-l > trans-d = cis-dach. The A2780/l-OHP selected for trans-l resistance is 3.6-fold resistant to oxaliplatin, showed no resistance to trans-d isomer and is 6-fold resistant to cis-dach. However, L1210/dach which is selected for carboxyphthalato 1,2-dach (trans-dl) platinum(II) is 140-fold resistant to oxaliplatin, 73-fold resistant to trans-d, and 41-fold resistant to cis-OHP. The accumulation and DNA binding of platinum following a 2-h treatment of A2780 cells with each of the isomers (60 microM) is in the order of trans-l > cis-dach > trans-d which corresponded to the cytotoxicity of trans-l, but not the others. The data suggest that other processes, such as differential formation of specific adducts and/or repair may be involved. Of the three isomers l-OHP is the superior and its accumulation and DNA binding are consistent with its cytotoxicity.
Animals↗
Intracellular glutathione and cytotoxicity of platinum complexes.
Although there have been a number of reports correlating cellular GSH levels with cytotoxicity of platinum agents, none has examined the relationship between GSH concentrations and cytotoxicity. In this study, using a highly specific HPLC method for measuring GSH and expressing GSH as concentration and also per cell number, we evaluated the correlation between GSH levels and the cytotoxicity to five agents in ten human tumor cell lines. The five platinum agents included the platinum(II) complexes cisplatin, carboplatin and oxaliplatin and platinum(IV) complexes iproplatin and tetraplatin. The correlation between intracellular GSH concentration and cytotoxicity was highly significant only for iproplatin (P = 0.002) followed by tetraplatin, which demonstrated a trend toward statistical significance (P = 0.06). Cytotoxicity of the other platinum complexes showed no relation to GSH concentration, cisplatin itself showing a P-value of 0.09. In contrast, the GSH levels normalized to cell number showed a statistically significant correlation with the cytotoxicity of four of the five platinum agents, the exception being carboplatin; the strongest correlation observed was that for iproplatin and tetraplatin. Glutathione-S-transferase (GST) activity in these cell lines showed no correlation with cytotoxicity of any of the platinum complexes. Our results, from the analyses of both GSH concentration as well as GSH per cell number, suggest a significantly higher interaction between GSH and iproplatin compared with the other platinum agents. Moreover, our data suggest that relationships between cytotoxicity and GSH levels on a per-cell basis may not persist when differences in cell volume are taken into account.
Antineoplastic Agents↗
Karyotype evolution in holocentric chromosomes of three related species of triatomines (Hemiptera-Reduviidae).
C-banded karyotypes, DNA content and the male meiiotic process of Triatoma platensis and Triatoma delpontei are compared with those of Triatoma infestans, the main vector of Chagas disease in South America. These three species present the same diploid chromosome number 2n = 22 (20 autosomes + XX male/XY female). They also have several cytogenetic traits that differ from all other triatomines: large autosomes, C-heterochromatic blocks and meiotic heteropycnotic chromocenters formed by autosomes and sex chromosomes. In spite of these similarities, each species presents different chromosomal behavior during male meiosis, distinct DNA content and a specific amount and localization of the C-heterochromatin. The differences in DNA content are mainly due to the variation in C-heterochromatin amount, which may be interpreted as loss and/or gain of C-regions. This interpretation is supported by the presence of meiotic and mitotic chromocenters that facilitate the transference of C-positive material. The cytogenetic data presented in this work suggest that T. infestans and T. platensis are more closely related to each other than to T. delpontei. It can also be inferred that the differences in distribution and amount of heterochromatin do not play a direct role in speciation in this group.
Animals↗
Changes in brain, plasma and cerebrospinal fluid contents of beta-endorphin in dogs at the moment of death.
To investigate the possible participation of endogenous opioids in the cerebral events that take place at the moment of death we studied brain, cerebrospinal fluid and serum contents of beta-endorphin in dogs that were either conscious or unconscious at the moment of sudden death induced by cardiac arrest. Although with great interindividual variations, the animals that were conscious at the moment of cardiac arrest, presented a significant increase in beta-endorphin when compared with their own previous values (p < 0.05) or with the values found in animals that were deeply anaesthetized at the time of cardiac arrest. There seems to be a sudden increment of beta-endorphin in brain tissue and body fluids of dogs who are conscious at the moment of sudden death, this change was not observed in dogs that were anaesthetized prior to death. Brain opioids could participate in the sensations narrated by subjects in the so called near-death experience.
Animals↗
Reversibility of the alterations induced by chronic alcoholism and malnutrition in rats after alcohol withdrawal and proper nutrition.
OBJECTIVE: The specific influence of malnutrition on the cellular damage induced by alcoholism has been poorly defined; therefore, the possible degree of improvement that could be obtained after the institution of proper nutrition and after alcohol withdrawal remains unclear. We studied both conditions in several combinations, either after chronic alcoholism, chronic malnutrition or both, and after reversal of each condition or of both. METHOD: Using experimental models of alcoholism and malnutrition, we studied the alterations induced by each condition and on the combination of both in five histological locations and in 10 hematological and biochemical parameters; afterwards, we studied the possible restorative effect on each parameter after 4 months of alcohol withdrawal or proper nutrition or both. RESULTS: Our results showed that chronic alcoholism induced a mean of 31% deviation from values obtained in controls, malnutrition induced 17%, and alcoholism and malnutrition combined induced 52%. Upon the removal of the offending condition, alcohol withdrawal brought 13% improvement and proper nutrition 5% improvement; in the animals with alcoholism and malnutrition, alcohol withdrawal and proper nutrition brought 26% improvement, alcohol withdrawal but continuation of malnutrition 10% improvement, and continuation of alcoholism but proper nutrition led to a further 8% worsening from the alterations already found during alcoholism and malnutrition. CONCLUSIONS: Multivariate statistical comparisons demonstrated that chronic malnutrition produced an important, independent and difficult to reverse effect on the damage induced by alcoholism in several histological and physiological parameters.
Alcoholism↗
Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer.
An ongoing phase I and pharmacokinetic trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin is evaluating the maximum tolerated dose (MTD) of a 3-hour paclitaxel infusion combined with fixed doses of carboplatin in previously treated and untreated patients with a variety of advanced cancers. A patient's previous treatment status determines the fixed carboplatin dose: target area under the concentration-time curves of 4.0 and 4.5 mg.min/mL in previously treated and untreated patients, respectively. Studies 1 and 2 entered previously treated patients to establish the paclitaxel MTD without and with cytokine support: study 1 established 135 mg/m2 paclitaxel as the MTD without such support. In study 2, granulocyte colony-stimulating factor is administered, and the MTD has not yet been reached with paclitaxel doses of 135 mg/m2 to 230 mg/m2 assessed thus far and 250 mg/m2 now being evaluated. Objective responses have been seen in three of five patients with squamous cell carcinoma of the head and neck and in patients with non-small cell lung cancer and metastatic cancer of unknown primary site as well. Myelosuppression has been the dose-limiting toxicity, although significant nausea and vomiting and myalgia have been documented occasionally. Paclitaxel apparently has nonlinear pharmacokinetics with a beta half-life of 6.7 hours (SD +/- 1.3 hours). Future trials of paclitaxel/carboplatin will address the management of squamous cell carcinoma of the head and neck and non-small cell carcinoma of the lung.
Adenocarcinoma↗
Effect of warm ischemia on insulin secretion in non-heart-beating donors.
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Animals↗