Biomedical subjects

A Galán

Publications and source records attributed to A Galán.

At least 19 recordsLinked to original sources

PubMed2006

XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer.

The purpose of this phase II trial was to determine the efficacy and safety of the XELOX (capecitabine/oxaliplatin) regimen as first-line therapy in the elderly patients with metastatic colorectal cancer (MCRC). A total of 50 patients with MCRC aged > or = 70 years received oxaliplatin 130 mg m(-2) on day 1 followed by oral capecitabine 1000 mg m(-2) twice daily on days 1-14 every 3 weeks. Patients with creatinine clearance 30-50 ml min(-1) received a reduced dose of capecitabine (750 mg m(-2) twice daily). By intent-to-treat analysis, the overall response rate was 36% (95% CI, 28-49%), with three (6%) complete and 15 (30%) partial responses. In total, 18 patients (36%) had stable disease and 14 (28%) progressed. The median times to disease progression and overall survival were 5.8 months (95% CI, 3.9-7.8 months) and 13.2 months (95% CI, 7.6-16.9 months), respectively. Capecitabine was well tolerated: grade 3/4 adverse events were observed in 14 (28%) patients: 11 (22%) diarrhoea, eight (16%) asthenia, seven (14%) nausea/vomiting, three (6%) neutropenia, three (6%) thrombocytopenia, and two (4%) hand-foot syndrome. There was one treatment-related death from diarrhoea and sepsis. In conclusion, XELOX is well tolerated in elderly patients, with respectable efficacy and a meaningful clinical benefit response. Given its ease of administration compared with combinations of oxaliplatin with 5-FU/LV, it represents a good therapeutic option in the elderly.

Age Factors↗

PubMed2006

Docetaxel and mitomycin as second-line treatment in advanced non-small cell lung cancer.

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of docetaxel and mitomycin C as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-eight patients with histologically confirmed, locally advanced or metastatic NSCLC were included in this phase II trial. All patients had been previously treated with a platinum-based regimen. Treatment consisted of docetaxel (75 mg/m2) followed by mitomycin C (8 mg/m2) on day 1, every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 courses of docetaxel-mitomycin C were administered (median five courses per patient). This combination was well tolerated with grade 3-4 toxicity experienced with the following frequency: neutropenia in five patients (13%), fatigue in four (11%), anaemia, thrombocytopenia, nausea/vomiting and peripheral neuropathy in one each (3%). Three of 38 patients had a partial response (8%, 95% confidence interval 2.6-21.6%), 14 patients (37%) experienced stabilization of disease and 21 (55%) had disease progression. Median time to progression was 3.6 months. Overall median survival was 10.4 months, with the 1-year actuarial survival rate being 35%. CONCLUSIONS: The addition of mitomycin C to docetaxel as second-line therapy in NSCLC is well tolerated but does not seem to improve the response rate.

Adult↗

PubMed2006

Ophthalmoscopic characteristics in sheep and goats: comparative study.

The ocular fundus was examined in 40 goat eyes and 40 sheep eyes by studying ophthalmoscopic characteristics and retinograms. Similarities and differing characteristics were described. In common: tapetal colour; peripheral yellowish area surrounding the Winslow stars; unpigmented areas in the non-tapetal zone; a great amount of myelin in the optic disc; the Bergmeister's papilla and the holoangiotic retinal vascular pattern. Differences: big size of the Winslow stars in goats; myelinizated fibre over the non-tapetal zone in sheep; shape, position and myelin distribution of the optic disc; and the presence of a 'primary artery' in goats.

Animals↗

PubMed2006

CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that frequently first presents in the skin.

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is an aggressive and rare preculsor hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to affect elderly patients, who usually present with skin lesions but often have a disseminated disease, including bone marrow involvement. Although the lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a relationship to plasmacytoid dendritic cells. Because of the rarity of this disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.

Aged↗

PubMed2005

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial.

BACKGROUND: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. PATIENTS AND METHODS: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. RESULTS: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010]. CONCLUSIONS: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.

Adult↗

PubMed2003

Implantation rates after two, three, or five days of embryo culture.

Extended embryo culture together with amelioration of embryo selection methods and embryo culture conditions have allowed a substantial increase on both pregnancy and implantation rates. However, uterine embryo transfers are still performed after 2 to 6 days of egg retrieval. In this paper, we show the results of two studies, one prospective study comparing IVF outcome of day 2 and day 3 embryo transfers, and a retrospective study looking at blastocyst transfers versus day 3 embryo transfers in our egg donation program. Also, we test the predictive value of the presence of three or more seven cell-stage embryos on day 3 of development on blastocyst formation and pregnancy rates. No significant differences were found between day 2 and day 3 embryo transfers in terms of pregnancy, ongoing pregnancy, and implantation rates, as well as in multiple and in high order pregnancy. In general, day 6 embryo transfers resulted in significantly higher ongoing pregnancy and implantation rates compared with day 3 embryo transfers (41.1 per cent and 23.6 per cent versus 50.1 per cent and 38.1 per cent, respectively). No differences were found in terms of multiple gestations despite transferring significantly more embryos on day 3 compared with day 6 transfers. When less than three 7-cell embryos were present in the embryo cohort, day 6 embryo transfers did not improve the rates of ongoing pregnancy with regards to day 3 embryo transfer, although significant high implantation rates were obtained on the group of blastocyst transfer. The presence of three or more 7 cell-stage embryos improved significantly both ongoing pregnancy and rates on blastocyst transfers compared to day 3 embryo transfers (65.6 per cent versus 50.6 per cent and 37.4 per cent vs 24.7 per cent, respectively). In conclusion, at least in egg donation, day 3 embryo transfers do not improve either pregnancy or implantation rates when compared to day 2 transfers. Generally speaking blastocyst transfers give significantly higher chance of pregnancy and implantation rates per cycle and per transfer than early cleavage stage transfers. However, the absence of a good embryo cohort, that is having less than three 7 cell-stage embryos on day 3, blastocyst transfers will improve implantation rates but not ongoing pregnancy rates.

Adult↗

PubMed2003

Multicenter phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) and raltitrexed are active against advanced colorectal cancer (ACC), act through different mechanisms, and have only partially overlapping toxicity profiles. Phase I studies have shown that single-agent full doses of both drugs can be safely combined. The aim of this multicenter study was to assess the efficacy and toxicity of the combination in patients with 5-fluorouracil (5-FU)-refractory ACC. PATIENTS AND METHODS: Between October 1999 and December 2000, 52 patients (31 males, 21 females) with a median age of 62 years (range 39-75) were included and received CPT-11 (350 mg/m(2) as a 60-min infusion) plus raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after CPT-11), with courses repeated every 21 days. Objective response was assessed after every three courses, and treatment maintained until tumor progression or unacceptable toxicity. RESULTS: A total of 313 cycles were administered, with a median of six cycles per patient (range 1-14). Seven patients (13.5%) achieved a partial response and one a complete response (1.9%), for an overall intention-to-treat response rate of 15.4% (95% confidence interval 6.1% to 27.2%). The incidence of grade 3/4 toxicity was 23.1% for diarrhea, 21.2% for asthenia, 17.3% for neutropenia, 13.4% for emesis and 7.7% for infection. There were no treatment-related deaths. With a median follow-up of 20 months, median survival was 11.9 months and median time to progression was 4.6 months. CONCLUSIONS: CPT-11 plus raltitrexed is active in patients with 5-FU-refractory ACC, at the expense of moderate toxicity.

Adult↗

PubMed2003

[Anterior uveitis and juvenile idiopathic arthritis].

PURPOSE: Anterior uveitis is one of the most important extraarticular manifestations of juvenile idiopathic arthritis (JIA). The aim of this study was to describe the frequency of uveitis, complications and ocular surgical procedures, to corroborate risk factors for the development of uveitis and to analyze its evolutive characteristics. METHODS: Retrospective review of 132 children diagnosed with JIA in our hospital from 1985 to 2000. Patients presenting anterior uveitis (Tyndall + or recent keratic precipitates) were studied. RESULTS: Uveitis was detected in 26 of 132 children (19%). All of them presented pauciarticular JIA. The patients received corticosteroid therapy for a mean time of 19.2 months, developing a mean of 4.5 episodes of uveitis. Patients diagnosed with uveitis before or within 1 year from the onset of arthritis required longer treatment (295 months versus 206) and suffered more episodes (73 versus 44) than those with uveitis found later on. Complications (cataract, band keratopathy, glaucoma, macular edema) developed in 27.9% of the affected eyes. Surgery was required in 10 eyes. CONCLUSIONS: The incidence of uveitis in our study is similar to recently reported rates. Female sex, pauciarticular onset, serum antinuclear antibodies (ANA) and early onset of uveitis seem to increase the development of chronic uveitis. Periodic slit-lamp ophthalmologic screenings in high risk patients are recommended (Arch Soc Esp Oftalmol 2003; 78: 561-566).

Arthritis, Juvenile↗

PubMed2001

Modulation of the stress response during apoptosis and necrosis induction in cadmium-treated U-937 human promonocytic cells.

Treatment for 2 h with 200 microM cadmium chloride, followed by recovery, caused apoptosis and induced heat-shock protein 70 (HSP70) expression in U-937 promonocytic cells. However, pre-incubation with the GSH depleting agent L-buthionine-[S,R]-sulfoximine (BSO, 1 mM for 24 h) caused necrosis instead of apoptosis and failed to induce HSP70 expression. This failure was a consequence of necrosis instead of GSH depletion, since BSO allowed or even potentiated HSP70 induction when used in combination with heat shock (2 h at 42.5 degrees C) or with 50 microM cadmium, which caused apoptosis. The administration of N-acetyl-L-cysteine (NAC) at the beginning of recovery after BSO/200 microM cadmium treatment prevented the execution of necrosis and restored the execution of apoptosis, but did not restore HSP70 induction, indicating that the inhibition by BSO of HSP70 expression is an early regulated event. This contrasted with the capacity of NAC to prevent the alterations caused by BSO/200 microM cadmium in other proteins, namely the suppression of Bax expression and the increase in Bcl-2 and HSP-60 expression. Finally, it was observed that treatment with 200 microM cadmium rapidly increased the HSP70 mRNA level and stimulated heat-shock factor 1 (HSF1) trimerization and binding, and that these effects were prevented by pre-incubation with BSO. Taken together, these results indicate that the stress response is compatible with apoptosis but not with necrosis in cadmium-treated promonocytic cells. The suppression of the stress response is specifically due to the early inhibition of HSF1 activation.

Acetylcysteine↗

PubMed2001

An analysis of spontaneous hatching in a human endometrial epithelial coculture system: is assisted hatching justified?

PURPOSE: To evaluate spontaneous embryo hatching in an endometrial epithelial coculture system, and compare it with cases where coculture was performed because of maternal age, previous repeated implantation failures, or both. To clarify in which cases assisted hatching would be appropriate. METHODS: Individual human embryos were cocultured on an endometrial epithelial cell monolayer until Day 6. RESULTS: Blastocyst hatching rate at Day 6, depending on maternal age, was 9.1% (age <37 years) and 3.4% (age > or = 37 years). However, blastocyst hatching rates depending on number of previous IVF failures were similar. CONCLUSIONS: Maternal age and previous implantation failures are factors affecting the ability of human embryos to reach the blastocyst stage in coculture. However, assisted hatching is not justified in these populations because of the absence of hatching rate differences between blastocysts obtained from these two groups and the control group.

Blastocyst↗

PubMed2001

The role of intracellular oxidation in death induction (apoptosis and necrosis) in human promonocytic cells treated with stress inducers (cadmium, heat, X-rays).

Treatment of U-937 human promonocytic cells with the stress inducers cadmium chloride (2 h at 200 microM), heat (2 h at 42.5 C) or X-rays (20 Gy), followed by recovery, caused death by apoptosis and stimulated caspase-3 activity. In addition, all stress agents caused intracellular oxidation, as measured by peroxide and/or anion superoxide accumulation. However, while pre-incubation with antioxidants (N-acetyl-L-cysteine or butylated hydroxyanisole) inhibited the induction of apoptosis by cadmium and X-rays, it did not affect the induction by heat-shock. Pre-incubation for 24 h with the GSH-depleting agent L-buthionine-[S,R]-sulfoximine (BSO) switched the mode of death from apoptosis to necrosis in cadmium-treated cells. By contrast, BSO only caused minor modifacions in the rate of apoptosis without affecting the mode of death in heat- and X-rays-treated cells. BSO potentiated peroxide accumulation in cells treated with both cadmium and X-rays. However, while the accumulation of peroxides was stable in the case of cadmium, it was transient in the case of X-rays. Moreover, the administration of antioxidants during the recovery period sufficed to prevent necrosis and restore apoptosis in BSO plus cadmium-treated cells. Cadmium and X-rays caused a decrease in intracellular ATP levels, but the decrease was similar in both apoptotic and necrotic cells. Taken together, these results demonstrate that (i) stress inducers cause intracellular oxidation, but oxidation is not a general requirement for apoptosis; and (ii) the duration of the oxidant state seems to be critical in determining the mode of death.

Adenosine Triphosphate↗

PubMed2000

Regulation of multidrug resistance 1 (MDR1)/P-glycoprotein gene expression and activity by heat-shock transcription factor 1 (HSF1).

Infection of HeLa cells with adenovirus-carrying HSF1(+) cDNA, which encodes a mutated form of HSF1 with constitutive transactivation capacity, increased multidrug resistance 1 (MDR1) mRNA level and P-glycoprotein (P-gp) cell surface content and stimulated rhodamine 123 accumulation and vinblastine efflux activity. On the other hand, infection with adenovirus-carrying HSP70 and HSP27 cDNAs did not increase MDR1/P-gp expression. HSF1 regulates MDR1/P-gp expression at the transcriptional level, since HSF1(+) bound the heat-shock consensus elements (HSEs) in the MDR1 gene promoter and also activated the expression of an MDR1 promoter-driven reporter plasmid (pMDR1(-1202)). In addition, heat-shock increased pMDR1(-1202) promoter activity but not the activity of a similar reporter plasmid with point mutations at specific HSEs, and the heat-induced increase was totally inhibited by co-transfection with an expression plasmid carrying HSF1(-), a dominant negative mutant of HSF1. The stress inducers arsenite, butyrate, and etoposide also increased pMDR1(-1202) promoter activity, but the increase was not inhibited (in the case of butyrate) or was only partially inhibited (in the case of arsenite and etoposide) by HSF1(-). These results demonstrate that HSF1 regulates MDR1 expression, and that the HSEs present in the -315 to -285 region mediate the heat-induced activation of the MDR1 promoter. However, other factors may also participate in MDR1 induction by stressing agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells.

Pulse treatment of U-937 promonocytic cells with cadmium chloride (2 h at 200 microM) provoked apoptosis and induced a rapid phosphorylation of p38 mitogen-activated protein kinase (p38(MAPK)) as well as a late phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). However, although the p38(MAPK)-specific inhibitor SB203580 attenuated apoptosis, the process was not affected by the ERK-specific inhibitor PD98059. The attenuation of the cadmium-provoked apoptosis by SB203580 was a highly specific effect. In fact, the kinase inhibitor did not prevent the generation of apoptosis by heat shock and camptothecin, nor the generation of necrosis by cadmium treatment of glutathione-depleted cells, nor the cadmium-provoked activation of the stress response. The generation of apoptosis was preceded by intracellular H(2)O(2) accumulation and was accompanied by the disruption of mitochondrial transmembrane potential, both of which were inhibited by SB203580. On the other hand, the antioxidant agent butylated hydroxyanisole-inhibited apoptosis but did not prevent p38(MAPK) phosphorylation. In a similar manner, p38(MAPK) phosphorylation was not affected by the caspase inhibitors Z-VAD and DEVD-CHO, which nevertheless prevented apoptosis. These results indicate that p38(MAPK) activation is an early and specific regulatory event for the cadmium-provoked apoptosis in promonocytic cells.

Apoptosis↗

PubMed2000

Uncoupling of apoptosis and Jun/AP-1 activity in human promonocytic cells treated with DNA-damaging and stress-inducing agents.

Earlier studies have indicated that Jun/AP-1 activity is associated with, and probably required for apoptosis induction by DNA-damaging and stress-inducing agents in human myeloid cells. To investigate this possibility, we examined the capacity of continuous treatments with etoposide (10 microM) and camptothecin (0.4 microM), and pulse treatments with X-rays (20 Gy), heat (2 h at 42.5 C) and cadmium chloride (2 h at 200 microM) followed by recovery, to provoke apoptosis and to simulate c-jun and c-fos expression and AP-1 binding in U-937 human promonocytic cells. All these treatments generated apoptosis with similar efficacy (50-60% apoptotic cells at 6 h of treatment or recovery). However, the capacity to increase c-jun and c-fos mRNA levels and to stimulate AP-1 binding was very different, ranging from more than a twelve-fold increase in the case of cadmium, to almost no increase in the case of heat-shock and etoposide. When the cells were pre-conditioned with a soft heat shock (1 h at 42 degrees C) the cadmium-provoked apoptosis was greatly inhibited, but the stimulation of AP-1 binding was not affected. The administration of cAMP-increasing agents also reduced the etoposide- and cadmium-provoked apoptosis. However, cAMP greatly stimulated c-jun and c-fos expression and AP-1 binding when applied together with etoposide (which itself was ineffective), and potentiated the cadmium-induced AP-1 binding. Conversely, retinoic acid abrogated the cadmium-provoked stimulation of AP-1 binding and transactivation capacity, and greatly inhibited the stimulation of binding caused by camptothecin and X-rays. However, retinoic acid did not inhibit the induction of apoptosis by these agents. These results indicate that Jun/AP-1 activity is not necessarily coupled with apoptosis, nor required for apoptosis induction by DNA-damaging and stress-inducing agents in human promonocytic cells.

Apoptosis↗

PubMed2000

The human blastocyst regulates endometrial epithelial apoptosis in embryonic adhesion.

The implanting blastocyst must appose and adhere to the endometrial epithelium and, subsequently, invade it. Locally regulated uterine epithelial apoptosis induced by the embryo is a crucial step of the epithelial invasion in rodents. To address the physiological relevance of this process in humans, we investigated the effect of single human blastocysts on the regulation of apoptosis in cultured human endometrial epithelial cells (hEEC) in both apposition and adhesion phases of implantation. Here, we report a co-ordinated embryonic regulation of hEEC apoptosis. In the apposition phase, the presence of a blastocyst rescues hEEC from the apoptotic pathway. However, when the human blastocyst adheres to the hEEC monolayer, it induces a paracrine apoptotic reaction. Fas ligand (Fas-L) was present at the embryonic trophoectoderm. Fas was localized at the apical cell surface of hEEC, and flow cytometry revealed that 60% of hEEC express Fas. Neutralizing adhesion assays revealed that the Fas/Fas-L death system may be an important mechanism to cross the epithelial barrier, which is crucial for embryonic adhesion, and the manipulation of this system could have potential clinical implications as an interceptive mechanism.

Apoptosis↗

PubMed2000

Embryonic regulation of endometrial epithelial apoptosis during human implantation.

Apoptosis is a mechanism of cell death in which cells undergo a genetically determined programme. The implanting blastocyst has to appose and adhere to the endometrial epithelium and subsequently invade it. Locally regulated uterine epithelial apoptosis induced by the embryo is a crucial step in epithelial invasion in rodents. To address the physiological relevance of this process in humans, we have investigated the effect of single human blastocysts on the regulation of apoptosis in cultured human endometrial epithelial cells (EEC) in the apposition and adhesion phases of implantation. We report a co-ordinated embryonic regulation of EEC apoptosis. In the apposition phase, the presence of a blastocyst rescues EEC from the apoptotic pathway. However, when the blastocyst adheres to the EEC monolayer it induces a paracrine apoptotic reaction.

Adhesiveness↗

PubMed1999

Conformational changes generated in GroEL during ATP hydrolysis as seen by time-resolved infrared spectroscopy.

Changes in the vibrational spectrum of the chaperonin GroEL in the presence of ADP and ATP have been followed as a function of time using rapid scan Fourier transform infrared spectroscopy. The interaction of nucleotides with GroEL was triggered by the photochemical release of the ligands from their corresponding biologically inactive precursors (caged nucleotides; P3-1-(2-nitro)phenylethyl nucleotide). Binding of either ADP or ATP induced the appearance of small differential signals in the amide I band of the protein, sensitive to protein secondary structure, suggesting a subtle and localized change in protein conformation. Moreover, conformational changes associated with ATP hydrolysis were detected that differed markedly from those observed upon nucleotide binding. Both, high-amplitude absorbance changes and difference bands attributable to modifications in the interaction between oppositely charged residues were observed during ATP hydrolysis. Once this process had occurred, the protein relaxed to an ADP-like conformation. Our results suggest that the secondary structure as well as salt bridges of GroEL are modified during ATP hydrolysis, as compared with the ATP and ADP bound protein states.

Adenosine Diphosphate↗

PubMed1999

ATP hydrolysis induces an intermediate conformational state in GroEL.

The conformational properties of the molecular chaperone GroEL in the presence of ATP, its non-hydrolyzable analog 5'-adenylimidodiphosphate (AMP-PNP), and ADP have been analyzed by differential scanning calorimetry (DSC), Fourier-transform infra-red (FT-IR) and fluorescence spectroscopy. Nucleotide binding to one ring promotes a decrease in the Tm value of the GroEL thermal transition that is reversed when both rings are filled with nucleotide, indicating that the sequential occupation of the two protein rings by these nucleotides has different effects on the GroEL thermal denaturation process. In addition, ATP induces a conformational change in GroEL characterized by (a) the appearance of a reversible low temperature endotherm in the DSC profiles of the protein, and (b) an enhanced binding of the hydrophobic probe 8-anilino-naphthalene-1-sulfonate (ANS), which strictly depends on ATP hydrolysis. The similar sensitivity to K+ of the temperature range where activation of the GroEL ATPase activity, the low temperature endotherm, and the increase of the ANS fluorescence are abserved strongly indicates the existence of a conformational state of GroEL during ATP hydrolysis, different from that generated on ADP or AMP-PNP binding. To achieve this intermediate conformation, GroEL mainly modifies its tertiary and quaternary structures, leading to an increased exposure of hydrophobic surfaces, with minor rearrangements of its secondary structure.

Adenosine Diphosphate↗