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Biomedical subjects

A Molina

Publications and source records attributed to A Molina.

At least 109 records · Page 6Linked to original sources
PubMed1997

Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection: an international study.

Association between mycosis fungoides (MF), its leukaemic variant Sezary syndrome (SS) and the human T-cell lymphotropic virus type-I (HTLV-I) has been controversial, with the reported incidence of infection varying between 0% and nearly 100%. We studied 127 patients (85 MF, 28 SS, five Sezary cell leukaemia, four lymphomatoid papulosis, and five unspecified cutaneous T-cell lymphomas (CTCL)) originating from Europe (France, Spain, U.K., Portugal) or from U.S.A. (California) for the presence of HTLV-I infection markers. HTLV-I and -II serology were performed on 78 patients using standard immunological methods. Reverse transcriptase (RT) assay was also performed in 26 cases using an RT-PCR-based method of high sensitivity. Molecular analyses were performed on 215 DNA samples (121 from fresh PBMCs, 26 from PBMCs after short-term culture and 68 from skin lesions) by PCR amplification using HTLV-I and -II gag, pol, env, pX and LTR specific primers. Immunological tests were negative except for two sera which were indeterminate. PCR with all HTLV-I and -II primer pairs showed negative results in all 215 samples investigated. No RT activity was detected in short-term PBMC cultures of any of the 26 cases studied. The results of this large study from five different countries clearly indicate that MF and SS are not associated with HTLV-I infection.

Blotting, Western↗
PubMed1997

Enhanced tolerance to bacterial pathogens caused by the transgenic expression of barley lipid transfer protein LTP2.

Purified lipid transfer protein LTP2 from barley applied on tobacco leaves eliminated symptoms caused by infiltration of Pseudomonas syringae pv. tabaci 153. Growth of the pathogen in leaves of transgenic tobacco plants was retarded when compared with non-transformed controls. The percentage of inoculation points that showed necrotic lesions was greatly reduced in transgenic tobacco (17-38% versus 78%) and the average size of these lesions was 61-81% that of control. The average total lesion area (necrosis and chlorosis) in the transgenic plants was also reduced (38% of control). Arabidopsis thaliana transgenic plants inoculated with P. syringae pv. tomato DC3000 also had lower percentages of necrotic lesions (22-38% versus 76%), a reduced average area for each lesion (53-67% of control), and a smaller total lesion area per inoculation (43% of control). These results further support the assignment of a defense role for LTPs and highlight their biotechnological potential.

Arabidopsis↗
PubMed1997

Vitamin B6 suppresses growth and expression of albumin gene in a human hepatoma cell line HepG2.

The effect of vitamin B6 on the growth of a human hepatoma cell line HepG2 in culture was studied. The growth of HepG2 cells and protein synthesis were almost completely inhibited in medium supplemented with 5 mM pyridoxine. Pyridoxal was as effective as pyridoxine, but pyridoxamine showed no inhibitory action. The growth inhibition of HepG2 cells by pyridoxine was accompanied by a marked inhibition of secretion of plasma proteins, particularly albumin. Northern blot analysis of albumin mRNA showed that pyridoxine caused a rapid decrease in the expression of albumin gene. The electron-microscopic examination of pyridoxine-treated HepG2 cells revealed a smoothing of nuclear membrane, a decrease in the number of nucleoli, and an appearance of aggregated heterochromatin structures. These morphological features are compatible with the depressed transcriptional activity in the pyridoxine-treated cells. The mechanism by which vitamin B6 exerts its inhibitory effect was discussed in terms of our recent finding that vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding proteins. Binding of pyridoxal phosphate with tissue-specific transcription factors may reduce the capacity of these factors to interact with the regulatory region of albumin gene, resulting in the inhibition of the gene expression.

Blotting, Northern↗
PubMed1997

High-dose chemotherapy and stem-cell rescue in the treatment of high-risk breast cancer: prognostic indicators of progression-free and overall survival.

PURPOSE: To examine the predictive value of tumor- and treatment-specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high-grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.

Adult↗
PubMed1996

Interleukin-2 (IL-2) and IL-6 regulate c-fos protooncogene expression in human pituitary adenoma explants.

We have previously shown that interleukin-2 (IL-2) and IL-6, which are expressed in the anterior pituitary, affect anterior pituitary cell proliferation in normal rats and cell lines. Here we examined their effects on the c-fos expression by human anterior pituitary adenomas. Adenoma cells in culture do not express c-fos mRNA. In adenoma explants, however, c-fos expression was detected and was regulated by IL-2 or IL-6. In different tumors (ACTH-, PRL-, GH-secreting and non functioning adenomas), these interleukins had inhibitory or stimulatory effects but the kind of response does not seem to be associated to tumor type or size. Using blocking antibodies, we observed that intrinsic IL-2 and IL-6 regulate c-fos expression in the same way. Our data suggest that IL-2 and IL-6 are not only involved in the regulation of pituitary adenoma function but may also, given the role of c-fos in cell proliferation, be implicated in the development of human pituitary adenomas.

Adenoma↗
PubMed1996

Synthesis of a photoaffinity labeling analogue of the inactivating peptide of the Shaker B potassium channel.

A photoactivatable derivative of the inactivating peptide of the Shaker B potassium channel (ShB peptide) has been synthesized from ShB peptide containing an added cysteine residue at the peptide carboxy-terminus and 1-(p-azidosalicylamido)-4-(iodoacetamido)butane. The peptide derivative restores rapid inactivation in the deletion mutant Shaker Bdelta6-46 potassium channel in a manner indistinguishable from that of the wild-type ShB peptide. Also, both peptides display similar conformational behavior when challenged in vitro by an artificial model target that partly imitates the properties of the putative receptor site for the inactivating peptide in the Shaker B potassium channel. Therefore, we conclude that both functionally and conformationally the photoreactive peptide derivative is an adequate analogue of the wild-type ShB peptide, suitable for photoaffinity labeling of its binding site in the Shaker B potassium channel. Moreover, because the ShB peptide also serves as an efficient inactivating peptide for a large variety of other potassium channels, it appears that the photoreactive analogue may be useful to explore homologous sites in many different channel proteins.

Affinity Labels↗
PubMed1996

Two cold-inducible genes encoding lipid transfer protein LTP4 from barley show differential responses to bacterial pathogens.

The barley genes HvLtp4.2 and HvLtp4.3 both encode the lipid transfer protein LTP4 and are less than 1 kb apart in tail-to-tail orientation. They differ in their non-coding regions from each other and from the gene corresponding to a previously reported Ltp4 cDNA (now Ltp4.1). Southern blot analysis indicated the existence of three or more Ltp4 genes per haploid genome and showed considerable polymorphism among barley cultivars. We have investigated the transient expression of genes HvLtp4.2 and HvLtp4.3 following transformation by particle bombardment, using promoter fusions to the beta-glucuronidase reporter sequence. In leaves, activities of the two promoters were of the same order as those of the sucrose synthase (Ss1) and cauliflower mosaic virus 35S promoters used as controls. Their expression patterns were similar, except that Ltp4.2 was more active than Ltp4.3 in endosperm, and Ltp4.3 was active in roots, while Ltp4.2 was not. The promoters of both genes were induced by low temperature, both in winter and spring barley cultivars. Northern blot analysis, using the Ltp4-specific probe, indicated that Xanthomonas campestris pv. translucens induced an increase over basal levels of Ltp4 mRNA, while Pseudomonas syringae pv. japonica caused a decrease. The Ltp4.3-Gus promoter fusion also responded in opposite ways to these two compatible bacterial pathogens, whereas the Ltp4.2-Gus construction did not respond to infection.

Antigens, Plant↗
PubMed1996

Polymyositis as a manifestation of chronic graft-versus-host disease.

A syndrome indistinguishable from idiopathic polymyositis occurred in 11 patients as a manifestation of chronic GVHD. All patients had elevation of creatine phosphokinase (CPK). Immunohistology demonstrated the effector cells in the muscle infiltrates as cytotoxic T cells, a finding similar to idiopathic polymyositis. Polymyositis is a rarely reported complication of chronic graft-versus-host disease (GVHD) with only 8 cases described in the literature. We encountered this syndrome in a small but significant percentage of our patients with chronic GVHD. Polymyositis associated with chronic GVHD does not affect the overall prognosis for the patient. Moreover, polymyositis can be the only manifestation of chronic GVHD. Awareness of this complication is important because it can be confused with other causes of muscle weakness after bone marrow transplantation. Finally, prompt initiation of corticosteroid therapy results in a rapid improvement of the associated symptoms.

Adolescent↗
PubMed1996

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

Adolescent↗
PubMed1996

Soluble adhesion molecules in renal transplantation.

Serum levels of sICAM-1 and sVCAM-1 adhesion molecules as well as TNF cytokine were measured in 50 kidney transplant recipients [14 patients with stable graft function, 18 patients with acute rejection, 10 patients with CsA toxicity, 6 patients with ATN, and 2 patients with cytomegalovirus (CMV) disease] during the first 3 postoperative weeks. All the patients studied showed, on the first posttransplant day, elevated serum levels of sICAM-1 (260 +/- 53 ng/mL). Interestingly, all the patients with good graft function presented thereafter a reduction of sICAM-1 serum levels close to the normal values (185.2 +/- 40 ng/mL). In contrast, the group of patients with acute allograft rejection showed significantly increased serum levels of sICAM-1 (371.5 +/- 86 ng/mL; p < 0.001), 3-4 days before diagnosis of acute rejection. Although sVCAM-1 levels were increased in both acute graft rejection (2263 +/- 106) and CsA toxicity (1650 +/- 315) patients, such increase was not significant among either group of patients when the group with CsA toxicity was compared with either ATN (1320 +/- 204) or stable renal function (1089 +/- 167). No statistical differences in the levels of TNF were demonstrated between the different groups of patients studied. Our findings demonstrate that quantitative determination of serum sICAM-1 may be of predictive clinical value in transplanted patients with acute renal allograft rejection.

Cyclosporine↗
PubMed1996

Prevention of recurrent esophageal bleeding and survival in patients with alcoholic cirrhosis: a randomized study.

OBJECTIVES: To compare endoscopic sclerotherapy, propranolol and distal splenorenal shunt in the prevention of rebleeding esophageal varices and mortality in alcoholic cirrhotics. METHODS: Forty-three alcoholic cirrhotics that had bled from esophageal varices were randomized to sclerotherapy (13), shunt (15) or propranolol(15). Outcomes measured were rebleeding from varices and death. RESULTS: There was no significant difference between the three treatment groups in relation to rebleeding rate or death. Continued alcohol consumption did not influence outcome. CONCLUSIONS: All three therapies were equally effective in preventing rebleeding from varices.

Adult↗
PubMed1995

Thalidomide as salvage therapy for chronic graft-versus-host disease.

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.

Adolescent↗
PubMed1995

The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate, and prednisone.

Graft-versus-host disease (GVHD) is a major obstacle to successful bone marrow transplantation (BMT) from matched unrelated donor (MUD). Currently available HLA-A, -B, and -DR serologic testing may not be sensitive enough to detect clinically relevant donor/recipient (D/R) nonidentity. Better HLA matching of D/R pairs using molecular typing for class II antigens in combination with intensive GVHD prophylaxis may potentially reduce the incidence of GVHD and lead to an improved outcome of MUD transplantation. Between July 1991 and August 1993, thirty consecutive patients with hematologic malignancies underwent MUD transplantation from donors who were identical for HLA -A, -B, and -DR by serologic typing. Twenty-five D/R pairs were matched for DRB and DQB by molecular typing (restriction fragment-length polymorphism and sequence-specific oligonucleotide probe hybridization analyses), whereas five were allele mismatched at either DRB or DQB. All patients also received GVHD prophylaxis with the combination of cyclosporine (CSA), methotrexate (MTX), and prednisone (PSE). The median age was 35 years (range, 15 to 50). The diagnoses were: chronic myelogenous leukemia (CML) in chronic phase (CP) (16), CML in more than CP (3), acute leukemia in more than first complete remission (CR) (8), acute leukemia in first CR (1), and advanced high-grade lymphoma (2). The preparative regimen consisted of 1,320 cGy fractionated total body irradiation (FTBI) and 60 mg/kg cyclophosphamide (CY) daily for 2 days in 17 good-risk patients (CML/CP and acute leukemia first CR); and 1,320 cGy FTBI in combination with 60 mg/kg etoposide and 20 to 60 mg/kg CY in 13 patients with advanced leukemia and lymphoma. All patients received CSA, PSE, and MTX on days 1, 3, 6 for GVHD prophylaxis, and 10 patients also received day +11 MTX. All patients engrafted except one who died early of regimen-related toxicity. The incidence of grade III or IV acute GVHD was 24% (95% confidence interval [CI], 10% to 44%) and that of extensive chronic GVHD was 65% (95% CI, 43% to 84%). At a median follow-up of 13.6 months, 57% of the patients are alive in remission with a median Karnofsky performance status of 90%. The cumulative probability of 2-year disease-free survival for all patients was 53% (95%) CI, 33% to 71%); for good-risk patients, 71% (95% CI, 46% to 87%) and for the poor-risk group, 34% (95% CI, 13% to 64%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors.

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty-two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty-three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno-occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high-dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.

Actuarial Analysis↗
PubMed1995

The defensive role of nonspecific lipid-transfer proteins in plants.

Plant nonspecific lipid-transfer proteins stimulate the transfer of a broad range of lipids between membranes in vitro. In view of their ability to inhibit bacterial and fungal pathogens, their distribution at high concentrations over exposed surfaces and in the vascular system, and the response of Ltp-gene expression to infection with pathogens, they are now thought to be active plant-defense proteins.

Bacteria↗
PubMed1995

Passive dual immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta maximally ameliorates acute aminonucleoside nephrosis.

Rats receiving a single dose (10 mg/100 g) of aminonucleoside of puromycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted both TNF-alpha and IL-1 beta cytokines. TNF-alpha secretion was first and maximally detected on day 3, whereas IL-beta activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo treatment with either anti-TNF-alpha or anti-IL-1 beta antibodies produced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstrate the effectiveness of immunosuppressive therapy against these two cytokines in rats with PAN-induced nephrosis.

Animals↗