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J Mendoza

Publications and source records attributed to J Mendoza.

At least 19 recordsLinked to original sources
PubMed2002

ELISA test to detect Chlamydophila pneumoniae IgG.

A new ELISA test (Chlamydophila pneumoniae IgG, Vircell, Spain) to detect Chlamydophila pneumoniae IgG was evaluated. The micro-immunofluorescence (MIF) test was used as reference method. Chlamydia trachomatis and Chlamydophila psittaci elementary bodies were also assayed. Two hundred and sixteen sera were included in the study: 66 from patients with peripheral arterial occlusive disease (Panel 1), 68 from adults with pneumonia (Panel 2), 44 from healthy adults (Panel 3) and 38 from patients with a sexuality transmitted disease by C. trachomatis (Panel 4). In Panel 1, 51 sera (77%) had antibody titres between 32 and 128; 4 out of 15 sera with IgG titres < 32 were positive by ELISA test and 2 sera with 32 IgG titres were uncertain by ELISA; the remaining 60 sera were correctly classified, giving a 91% concordance between the techniques. In Panel 2, 55 sera (81%) had IgG titres between 32 and 512; 2 out of 13 sera with IgG titres < 32 were positive by ELISA and 2 sera with 32 titres were uncertain by ELISA; the remaining 64 sera were correctly classified, giving a 97% concordance. In Panel 3, 22 sera (50%) had IgG titres between 32 and 64; only 1 out of 22 sera with IgG titres < 32 was positive by ELISA, giving a 97% concordance between the techniques. In Panel 4, there were 24 (63%) negative, 10 (26%) uncertain and 4 (10%) positive results by ELISA, giving an 86% concordance. The C. pneumoniae ELISA test demonstrated 100% sensitivity and 85% specificity. The IgG ELISA test demonstrated a good concordance with the MIF test without the drawbacks associated with the latter assay. We conclude that the ELISA test could be an alternative to the MIF test.

Antibodies, Bacterial↗
PubMed2001

P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions.

The ookinete surface proteins (P25 and P28) are proven antimalarial transmission-blocking vaccine targets, yet their biological functions are unknown. By using single (Sko) and double gene knock-out (Dko) Plasmodium berghei parasites, we show that P25 and P28 share multiple functions during ookinete/oocyst development. In the midgut of mosquitoes, the formation of ookinetes lacking both proteins (Dko parasites) is significantly inhibited due to decreased protection against lethal factors, including protease attack. In addition, Dko ookinetes have a much reduced capacity to traverse the midgut epithelium and to transform into the oocyst stage. P25 and P28 are partially redundant in these functions, since the efficiency of ookinete/oocyst development is only mildly compromised in parasites lacking either P25 or P28 (Sko parasites) compared with that of Dko parasites. The fact that Sko parasites are efficiently transmitted by the mosquito is a compelling reason for including both target antigens in transmission-blocking vaccines.

Animals↗
PubMed2001

[Can the Brucellacapt test be substituted for the Coombs test in the diagnosis of human brucellosis?].

BACKGROUND: Throughout this work we have studied the capacity of Brucellacapt test to replace Coombs test in the serological diagnosis of human brucellosis. METHODS: A total of 66 initial sera from patients with diagnostic of brucellosis were studied. The patients were divided in two groups: 42 patients showing a primo-infection (group1), and 24 patients with a previous case of brucellosis (group 2). As a controls, for the group 1 we have used 100 sera from healthy donors, and for group 2, 28 sera from people that have had clinical brucellosis but actually are in good health. All serum samples were tested in either Coombs and Brucellacapt tests. The diagnostic yield was calculated using ROC (receiver-operating characteristic) plots.Moreover, the results obtained in Coombs and Brucellacapt tests with 397 serum samples from 66 patients with brucellosis were compare with a non-parametric method. RESULTS: The sensibility and specificity for group1 were respectively 1 and 0.98 for Coombs and, 1 and 0.95 for Brucellacapt tests. For group 2, the results in Coombs test were 1 and 0.80, and in Brucellacapt test 0.95 and 0.74. In this second group, the area under the ROC plot was 0.950 for Coombs and 0.904 for Brucellacapt tests. Non statistical differences were observed comparing both serological tests using the Wilcoxon method (Z= -0.213; p=0.8). CONCLUSIONS: Brucellacapt and Coombs tests yield similar diagnostic results in the follow-up of serological samples from patients with brucellosis, and its should consider as interchangeables.

Brucellosis↗
PubMed2001

Knockout of the rodent malaria parasite chitinase pbCHT1 reduces infectivity to mosquitoes.

During mosquito transmission, malaria ookinetes must cross a chitin-containing structure known as the peritrophic matrix (PM), which surrounds the infected blood meal in the mosquito midgut. In turn, ookinetes produce multiple chitinase activities presumably aimed at disrupting this physical barrier to allow ookinete invasion of the midgut epithelium. Plasmodium chitinase activities are demonstrated targets for human and avian malaria transmission blockade with the chitinase inhibitor allosamidin. Here, we identify and characterize the first chitinase gene of a rodent malaria parasite, Plasmodium berghei. We show that the gene, named PbCHT1, is a structural ortholog of PgCHT1 of the avian malaria parasite Plasmodium gallinaceum and a paralog of PfCHT1 of the human malaria parasite Plasmodium falciparum. Targeted disruption of PbCHT1 reduced parasite infectivity in Anopheles stephensi mosquitoes by up to 90%. Reductions in infectivity were also observed in ookinete feeds-an artificial situation where midgut invasion occurs before PM formation-suggesting that PbCHT1 plays a role other than PM disruption. PbCHT1 null mutants had no residual ookinete-derived chitinase activity in vitro, suggesting that P. berghei ookinetes express only one chitinase gene. Moreover, PbCHT1 activity appeared insensitive to allosamidin inhibition, an observation that raises questions about the use of allosamidin and components like it as potential malaria transmission-blocking drugs. Taken together, these findings suggest a fundamental divergence among rodent, avian, and human malaria parasite chitinases, with implications for the evolution of Plasmodium-mosquito interactions.

Amino Acid Sequence↗
PubMed2000

Maintenance of safer sexual behaviours: evaluation of a theory-based intervention for HIV seropositive men with haemophilia and their female partners.

A theory-based HIV risk-reduction intervention was developed for HIV-positive men with haemophilia and their HIV-negative female romantic partners. The intervention was based on Prochaska and DiClemente's Transtheoretical Model which describes behaviour change as an incremental, stage-based process. The intervention targeted both communication about safer sex and safer sex behaviours (consistent condom use or abstinence from vaginal intercourse). A total of 255 males and 158 females from six funded haemophilia treatment centres or patient organizations (and 27 associated subsites) participated in the study. Baseline and follow-up (15 months after baseline) measures were administered to assess safer sexual behaviours, communication about safer sex and condom self-efficacy. A quasi-experimental, repeated measures design was utilized to compare two naturally occurring groups; those who received the full intervention package and those who received incomplete or no intervention components. Significant intervention effects for safer sex behaviours, communication about safer sex and condom self-efficacy were identified for the male participants, with those receiving the full intervention package demonstrating better outcomes at follow-up. Women who received the full intervention package were more likely to report the use of a condom by their male partner during the last act of vaginal intercourse.

Adult↗
PubMed2000

Inhibition of the mosquito transmission of Plasmodium berghei by Malarone (atovaquone-proguanil).

Sera from patients treated with atovaquone-proguanil (Malarone) have previously been shown to inhibit the mosquito transmission of Plasmodium falciparum, though the inhibition was not complete and the effect declined 2 weeks after treatment. In marked contrast, the inhibition of transmission of P. berghei by human sera (fed to mosquitoes, with P. berghei gametocytes, via membrane feeders) from volunteers treated with atovaquone-proguanil was total up to day 28 post-treatment and still very significant at day 56. In view of the short half-lives of atovaquone and proguanil, this was unexpected, and further experiments, reported here, were undertaken. In contrast to the incomplete blockade of infectivity of P. falciparum by serum taken 4 days post-treatment, such serum was totally inhibitory against P. berghei at a 1:10,000 dilution, indicating a remarkable sensitivity of P. berghei and demonstrating an unusual difference between the two Plasmodium species in response to a drug. The inhibitory effect on P. berghei after day 4 was caused by atovaquone and mainly through blockade of development from ookinete to oocyst. Despite previous information on the rapid elimination of atovaquone by patients, the present data indicate that low concentrations of this drug may persist in the plasma for some weeks after treatment.

Animals↗
PubMed2000

Dependence of anticancer activity of camptothecins on maintaining their lactone function.

Camptothecins contain a lactone ring that exists in the closed form below ph 7. Above 7, the open (CPT+) and the closed (CPT) form coexist in a 50-50 ratio in mouse plasma and in a 90-10 ratio in human plasma due to the high affinity of human serum albumin (HSA) for CPT+. CPT+ is much less toxic than CPT and it is excreted much faster. In complete RPMI 1640 culture medium, the equilibrium CPT(+)-CPT is 50-50. If 4% HSA is added, it moves to 90-10 modeling for the human physiological situation.

Animals↗
PubMed2000

Structure-activity relationship of alkyl camptothecin esters.

The cytotoxicity of camptothecin (CPT) esters 1-6 was measured. Like parental camptothecin, esters 2 and 3, but not 1, 4, 5, and 6, inhibited proliferation of human leukemia cells in culture and induced programmed cell death as assessed by flow cytometry studies. Exhibition of similar levels of antiproliferative activities of CPT 2 and 3 required different incubation time periods in cell cultures, with CPT and 3 requiring the shortest and longest periods, respectively. Both 2 and 3 were inactive against cells resistant to the semisynthetic CPT derivative 9-nitrocamptothecin and unable to stabilize DNA-topoisomerase I (Topo I) "cleavable complexes" in a cell-free system, suggesting that Topo I activity was required but insufficient for the mechanism of action of 2 and 3. Mouse liver homogenate converted esters to parental CPT, but the conversion rates were different with different esters. Of four tested esters in this experiment, ester 2 had the fastest conversion rate. In vivo studies showed that ester 2 had an exceptional lack of toxicity in nude mice, even at enormous doses, and demonstrated extensive activity against human breast and colon tumors grown as xenografts in immunodeficient nude mice, whereas no antitumor activity was observed for the other esters. In conclusion, ester 2 is a prodrug of the antitumor compound CPT, and it can be administered at very high doses in mice with no appearance of toxicity. This study provides a basis for further evaluation of CPT ester 2 as an investigational anticancer agent.

Animals↗
PubMed2000

Pharmacology of camptothecin esters.

An intact lactone ring of camptothecins is a structural requirement for their anticancer activity. Propionate esters of camptothecin (CPT) and 9-nitrocamptothecin (9NC), CZ48 and CZ112, respectively, have been synthesized as derivatives resistant to lactone hydrolysis and are chemotherapeutically active. In this study, we have examined the mechanism of action of CZ48 and CZ112 and their distribution, metabolism, and toxicity. CZ112 incubated in human plasma retained its lactone structure longer than 9NC (t1/2: 10.5 and < 1 hr for CZ112 and 9NC, respectively). This resistance to lactone hydrolysis was also observed in mouse plasma or albumin solutions. Neither CZ48 nor CZ112 inhibit topoisomerase I and thus are prodrugs dependent on hydrolysis to CPT or 9NC, respectively. Rates of hydrolysis of CZ48 to CPT are higher by homogenates of mouse liver, spleen, lung, and kidney than by plasma. Rates of hydrolysis by tumor cells in culture vary and were higher by breast cancer and melanoma cells than by colon cancer cells. On the basis of these and other data, it is proposed that CZ48 and CZ112 may act as anticancer agents by resisting hydrolysis to camptothecins while in circulation. Hydrolysis in tissues may release intact lactone in target tissues.

Animals↗
PubMed1998

Acquisition of cellular resistance to 9-nitro-camptothecin correlates with suppression of transcription factor NF-kappa B activation and potentiation of cytotoxicity by tumor necrosis factor in human histiocytic lymphoma U-937 cells.

Resistance of tumor cells to chemotherapeutic agents is a major problem in cancer therapy. Continuous exposure of human histiocytic lymphoma U-937 cells to 9-nitro-camptothecin (9NC), an inhibitor of the nuclear DNA topoisomerase I, induces resistance to this drug. Because of the involvement of the nuclear factor NF-kappa B in the expression of several growth regulatory genes, we examined the activation of this transcription factor in 9NC-resistant U-937 cells. We found that resistance to increasing concentrations of 9NC correlated with resistance to tumor necrosis factor (TNF)-dependent activation of NF-kappa B. However, the constitutive synthesis of NF-kappa B proteins remained unaffected. Cellular resistance was not unique to TNF, as other activators of NF-kappa B, including interleukin-1, phorbol ester and hydrogen peroxide, also had no effect. There was no difference between 9NC-sensitive and -resistant cells in the activation of NF-kappa B by okadaic acid. Other transcription factors, including AP-1 and Oct-1, were not affected in the resistant cells. When examined for the inhibitory subunit of NF-kappa B (I kappa B alpha), resistant cells showed a faster rate of resynthesis than the control. Interestingly, although 9NC resistance correlated with resistance to TNF-dependent NF-kappa B activation, TNF-dependent cytotoxicity in these cells was enhanced by several hundred fold despite a significant decrease in the number of TNF receptors. In conclusion, our results suggest that NF-kappa B activation may play a role in tumor cell killing by 9NC but not by TNF.

Antineoplastic Agents↗
PubMed1997

Mechanisms of resistance in a human cell line exposed to sequential topoisomerase poisoning.

Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoisomerase II protein levels in cell lines resistant to camptothecin. In an effort to understand potential mechanisms of resistance to this strategy, we developed a U-937 cell subline, denoted RERC, that is capable of surviving exposure to sequential topoisomerase poisoning. The RERC cells are 200-fold resistant to camptothecin, 8-fold resistant to etoposide, and 10-fold hypersensitive to cisplatin compared to the parental U-937 cells. Biochemical analyses indicate that the resistant phenotype involves alterations in both topoisomerase I and topoisomerase IIalpha. Topoisomerase I catalytic activity in the resistant cells is similar to that of the parental line but is resistant to camptothecin. Moreover, the resistant cells express a single mRNA species of topoisomerase I that codes for a mutation in codon 533. In addition, topoisomerase IIalpha protein levels are decreased 10-fold in the resistant line, coincident with a two-fold decrease in the expression of topoisomerase IIalpha mRNA. Collectively, these results indicate that resistance to sequential topoisomerase poisoning may involve a reduction in total cellular topoisomerase activity.

Antineoplastic Agents↗
PubMed1997

Monocytic differentiation of HL-60 promyelocytic leukemia cells correlates with the induction of Bcl-xL.

Treatment of human promyelocytic leukemia HL-60 cells with phorbol esters ultimately induces the differentiation of these cells along the monocyte/macrophage lineage, whereas treatment with retinoic acid or DMSO induces granulocytic/neutrophillic differentiation. In this study, we demonstrate the disparate fates of HL-60 cells treated with the phorbol ester 12,13-phorbol dibutyric acid (PDBu) or DMSO. After DMSO treatment, HL-60 cells eventually died via apoptosis, whereas the viability of PDBu-treated cells was not affected during the same interval. The levels of the apoptosis effector proteins Bak and Bad were enhanced, whereas there was a slight down-regulation of the apoptosis suppressor protein Bcl-2 after treatment of the cells with PDBu and DMSO. Treatment with DMSO resulted in the elevation of the apoptosis effector Bax, whereas treatment with PDBu did not significantly alter the levels of this protein. However, treatment of HL-60 cells with PDBu induced the rapid expression of the apoptosis suppressor protein Bcl-xL, whereas the expression of this protein remained unaltered in DMSO-treated cells. The generality of this finding was confirmed by the induction of Bcl-xL in human myeloid U-937 cells, human peripheral blood monocytes exposed to phorbol ester, and mouse thioglycollate-activated and resident peritoneal macrophages. PDBu-treated HL-60 cells remained viable for 7 days and thereafter began to die via apoptosis, with a concomitant down-regulation of Bcl-xL. In conclusion, we propose that Bcl-xL expression is associated with differentiation and survival of hematopoietic cells along the monocyte/macrophage lineage.

Apoptosis↗
PubMed1997

[Diffuse lung involvement in primary amyloidosis as an infrequent cause of interstitial lung disease. Clinical case].

We report a 50 years old female, admitted to the hospital due to malaise lasting 7 months, with diffuse bilateral lung infiltrates and a progressive respiratory insufficiency, dying one month after admission. A transbronchial biopsy disclosed an extensive amyloid infiltration. The necropsy confirmed this finding and showed a systemic primary amyloidosis associated to a multiple myeloma.

Amyloidosis↗
PubMed1996

An assessment of factors affecting neurological recovery after spinal cord injury with vertebral fracture.

In order to assess some of the variables associated with neurological recovery after traumatic spinal cord injury with vertebral fracture, a randomised sample of 100 patients (50 without neurological recovery, and 50 with several degrees of recovery) were selected out of 245 patients admitted to our hospital. Both groups were homogeneous with respect to time lapse to admission, hospitalization time and level of lesion. Of the variables considered, the intensity of the lesion (incomplete) and vertebral displacement (under 30%) were statistically associated with neurological recovery. An age under 30 years at the moment of the injury was also associated with neurological recovery but only in those patients with an incomplete lesion. No correlation was found between the other variables studied such as the degree of vertebral wedging, type of fracture (compression, flexion-rotation) and management (conservative, surgical) and the neurological evolution.

Adult↗
PubMed1996

[Varicella complicated by pericarditis and pneumonia].

Varicella is a highly infectious disease mainly affecting young children under 14 years of age, and being generally mild. In adults immunodeficient children and neonates exposed in utero, the illness tends to be more severe with higher incidence of complications. The type of complication is linked to the age: in children, bacterial infection of skin lesions and acute cerebellar ataxia are more frequent while lower respiratory tract infection, Reye syndrome and encephalitis are less common. Varicella pneumonia is found typically in adult patients and diffuse encephalitis which course is worse than children could be less frequently. Acute pericarditis is an exceptional complication with a benign course, but only if myocarditis or pericardial effusion are not concurrent. It usually appears in teenagers and young adults; only a few times, it has been linked to other complications as pneumonia or arthritis. We report a varicella case in an adult patient who suffered from pneumonia and pericarditis, both of them were benign.

Acute Disease↗
PubMed1995

Growth inhibition of human cancer metastases by camptothecins in newly developed xenograft models.

Several metastatic models have been developed using clonal selection of human malignant cells metastasizing into a specific organ in NIH-I Swiss immunodeficient mice. The organs of choice were the central nervous system (CNS), targeted by metastases of malignant melanoma, and the liver, with metastases of colon adenocarcinoma. Additional models of adrenal metastases by malignant melanoma, and CNS involvement by implanted human lung squamous carcinoma or lymphoblastoid cells, are also available. Organ metastases, as well as the effects of treatment, were confirmed by autopsies and histological examination of the tissues or by a surgical inspection of the liver. The treatment end points were established as the increases in survival times of treated mice relative to placebo-treated controls. Camptothecins injected i.m. or delivered via gastrointestinal tract inhibit the growth of CNS metastases and increase the survival of treated animals. 9-Amino-20(S)-camptothecin was effective in the CNS model and in the model of liver metastases. The drug increased 3.3- and 5.7-fold the survival rates relative to untreated controls with metastases of colon adenocarcinoma to the liver, and all camptothecins were significantly more effective than 5-fluorouracil, currently a drug of choice in treatment of this disease. The xenograft models of metastases are available for studies of drug passage through the blood-brain barrier optimization of drug delivery to the liver, and for the development of new camptothecin-based treatment strategies.

Adenocarcinoma↗
PubMed1995

Sensitivity of camptothecin-resistant human leukemia cells and tumors to anticancer drugs with diverse mechanisms of action.

Human leukemia U-937 cell clones resistant to 9-nitrocamptothecin (9NC) appear after exposure to increase 9NC-concentrations. Drug resistance is irreversible, regardless of whether the 9NC-resistant (U-937/CR150) cells grow in media with or without 9NC. U-937/CR150 cells are more sensitive than wild type U-937 (U-937/wt) cells to topoisomerase II-directed drugs, amsacrine, daunorubicin, and etoposide. The mitotic inhibitor, vincristine, induces hyperdiploidy in U-937/wt, but not in U-937/CR150 cells, whereas the antimetabolites, cytarabine and methotrexate, and the nitrosourea, carmustine, elicit similar responses in both U-937/wt and U-937/CR150 cells. U-937/CR150-generated tumors in nude mice are sensitive to etoposide. The clinical implications of increased sensitivity of 9NC-resistant tumors to some anticancer drugs are discussed.

Animals↗