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J D Toledo

Publications and source records attributed to J D Toledo.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for a central apolipoprotein A-I domain loosely bound to lipids in discoidal lipoproteins that is capable of penetrating the bilayer of phospholipid vesicles.

Previous evidence indicated that discoidal reconstituted high density lipoproteins (rHDL) of apolipoprotein A-I (apoA-I) can interact with lipid membranes (Tricerri, M. A., Córsico, B., Toledo, J. D., Garda, H. A., and Brenner, R. R. (1998) Biochim. Biophys. Acta 1391, 67-78). With the aim of studying this interaction, photoactivable reagents and protein cleavage with CNBr and hydroxylamine were used. The generic hydrophobic reagent 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine gave information on the apoA-I regions in contact with the lipid phase in the rHDL discs. Two protein regions loosely bound to lipids were detected: a C-terminal domain and a central one located between residues 87 and 112. They consist of class Y amphipathic alpha-helices that have a different distribution of the charged residues in their polar faces by comparison with class A helices, which predominate in the rest of the apoA-I molecule. The phospholipid analog 1-O-hexadecanoyl-2-O-[9-[[[2-[125I]iodo-4-(trifluoro-methyl-3-H-diazirin-3-yl)benzyl]oxy]carbonyl]nonanoyl]-sn-glycero-3-phosphocholine, which does not undergo significant exchange between membranes and lipoproteins, was used to identify the apoA-I domain directly involved in the interaction of rHDL discs with membranes. By incubating either rHDL or lipid-free apoA-I with lipid vesicles containing 125I-TID-PC, only the 87-112 apoA-I segment becomes labeled after photoactivation. These results indicate that the central domain formed by two type Y helices swings away from lipid contact in the discoidal lipoproteins and is able to insert into membrane bilayers, a process that may be of great importance for the mechanism of cholesterol exchange between high density lipoproteins and cell membranes.

Amino Acid Sequence↗
PubMed2000

Cholesterol flux between lipid vesicles and apolipoprotein AI discs of variable size and composition.

Reconstituted discoidal high-density lipoproteins (rHDLs) of apolipoprotein AI are able to induce leakage of the internal aqueous space of lipid vesicles (A. Tricerri et al., 1998, Biochim. Biophys. Acta 1391, 67-78) and such interaction depends on the cholesterol content of vesicles and rHDL as well as the rHDL size. With the aim of knowing if this rHDL/vesicle interaction plays some role in the cholesterol exchange, the time course for bidirectional radiolabeled cholesterol transfer between 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) vesicles and different sized rHDLs was measured. The results show that size increase in the rHDL decreases the rate constant for cholesterol transfer from POPC/cholesterol vesicles and that the initial presence of cholesterol in the vesicles results in an increased rate constant for cholesterol transfer from the rHDLs. This cannot be explained by a simple aqueous diffusion mechanism. The existing correlation between rHDL/vesicle interaction and cholesterol transfer rate suggests that besides the aqueous diffusion, another mechanism involving the binding or interaction between donor and acceptor may occur. This fact may be of physiological relevance since the relative high affinity of small cholesterol-poor discs for cell membranes could facilitate the cholesterol efflux, while the decreased membrane affinity as a consequence of cholesterol enrichment and increase in size would decrease the rate of transfer in the opposite direction.

Apolipoprotein A-I↗
PubMed1998

Conformation of apolipoprotein AI in reconstituted lipoprotein particles and particle-membrane interaction: effect of cholesterol.

Discoidal recombinant high density lipoproteins (rHDL) of apolipoprotein AI (apoAI) and palmitoyloleoylphosphatidylcholine (POPC), with or without cholesterol, were prepared by cholate dialysis. By gel filtration, rHDL containing 2-4 (Lp2, Lp3 and Lp4) apoAI molecules/particle were obtained. The ApoAI conformation in these rHDL was investigated by tryptophan fluorescence, denaturation with guanidine HCl, and immunoreactivity with two monoclonal antibodies recognizing epitopes in the N-terminal and central domains. Data show that apoAI conformation is highly dependent on particle size as well as on cholesterol. The ability of rHDL to interact with lipid bilayer was studied by measuring leakage induction on POPC and POPC/cholesterol vesicles loaded with terbium/dipicolinic acid. Among the cholesterol-free rHDL, the most efficient ones were the smallest Lp2. Leakage induction on POPC vesicles is dramatically decreased by the presence of cholesterol in Lp2 and Lp3. All the rHDL, but specially those containing cholesterol, induced more leakage on the POPC/cholesterol than on the POPC vesicles. These results suggest that in small cholesterol-poor particles, apoAI could have a conformation determining a high affinity for membranes, which could facilitate cholesterol efflux. After cholesterol enrichment, a conformational change in apoAI could decrease the affinity for membranes allowing the lipoprotein release.

Antibodies, Monoclonal↗
PubMed1998

Thyroid hormones promote early metamorphosis in grouper (Epinephelus coioides) larvae.

The response of grouper larvae to the thyroid hormones, thyroxine (T4) and triiodothyronine (T3), was examined. Two-, 3-, and 4-week-old grouper larvae were reared in seawater containing either T4 or T3 at 0.01, 0.1, and 1 ppm. T4 or T3 induced metamorphosis in all age groups in a dose-dependent manner. Regardless of the size of the larvae, metamorphosis was completed in 2 days in larvae treated with 1 ppm of either T4 or T3; 3-4 days in larvae exposed to 0.1 ppm; and 5-6 days in larvae immersed in 0.01 ppm. None of the fish in the control group completed metamorphosis during this period. Compared with the control fish, survival rates were higher in groups exposed to 0.01 ppm and lower in those exposed to 1 ppm of T3. In 4-week-old larvae, T4 treatment (0.01 to 1.0 ppm) resulted in higher survival compared to the control. These results suggest that a dose of 0.01 ppm is appropriate for acceleration of metamorphosis and improvement of survival in 3- and 4-week-old grouper larvae. A lower dose may be apropriate for earlier stages.

Aging↗
PubMed1996

Malignant fibrous histiocytoma of the renal capsule and synchronous transitional cell carcinoma of the bladder.

The synchronous association of malignant fibrous histiocytoma (MFH) of the kidney and transitional cell carcinoma of the urinary bladder is reported. This constitutes the ninth case of MFH definitely arising from the renal capsule. Fever was its first clinical manifestation. Despite complete surgical removal, the tumor was rapidly fatal. The current literature about MFH of the kidney is extensively reviewed.

Aged↗
PubMed1994

Basaloid-squamous cell carcinoma of the larynx and hypopharynx. A clinicopathologic study of 7 cases.

During a 16-year period (1974-1989), a retrospective review of 468 surgical specimens of laryngectomy yielded 7 cases (0.66%) of basaloid-squamous cell carcinoma. They were all males between 42 and 63 years of age. Four cases were supraglottic and one transglottic. The other two arose in the left pyriform sinus and vallecula, respectively. At diagnostic time, 4 cases were Stage III and 2 Stage IV, only one being Stage II. Glanz index of histologic malignancy was high (> 5) in most cases (6/7). Mitotic rate was also high (22-78 mitoses/10 HPF). Lymph node metastases were documented at diagnosis in 5 cases, 3 of them presenting with extracapsular extension. One case developed liver metastases. During the follow-up, lymph nodes of the neck were again metastasized in 4 cases, and stomal recurrence was present in another one. Death of disease was confirmed in 5 cases after 10 to 35 months of follow-up. Overall survival was 28.5% after 3 years.

Adult↗
PubMed1994

Small cell carcinoma of the urinary bladder. A clinicopathological study of six cases.

OBJECTIVE: To study the clinical, histological, and immunohistochemical findings of small cell carcinoma (SCC) of the urinary bladder, and also to delineate its behaviour in comparison with transitional cell carcinomas of the bladder. MATERIALS AND METHODS: A retrospective review of 552 patients with bladder cancer yielded six cases (1%) of small cell carcinoma which were histologically identical to pulmonary small cell anaplastic carcinoma. Clinical data and follow-up were collected. Aside from the conventional histological parameters, an immunohistochemical study with AE1-AE3 and Cam 5.2 keratins, epithelial membrane antigen, neuron-specific enolase, chromogranin, synaptophysin, ACTH, calcitonin, and prostatic specific antigen was performed. RESULTS: The clinical presentation did not differ from conventional transitional cell carcinoma, haematuria being the most frequent complaint (four cases). All the cases presented as flat tumours. On light microscopy, there were oat cell (four cases), intermediate (one case) and mixed oat-cell/intermediate (one case) variants. Three cases were associated with transitional cell carcinoma. Dysplastic changes were observed in the adjacent urothelium in one case only. At the time of diagnosis, all tumours were deeply invasive (pT3). Three cases were Stage III and three Stage IV, with involvement of regional lymph nodes and metastases to the liver (two cases) and lung (one case). Immunohistochemically, epithelial markers were variably expressed as AE1-AE3 keratin (5/6), Cam 5.2 keratin (2/6) and epithelial membrane antigen (3/6). Neuron specific enolase was demonstrated in every case. Chromogranin, however, was expressed in only one case. Synaptophysin, ACTH, calcitonin, and prostatic specific antigen all gave negative results. All the patients died of the disease and the overall length of survival was very poor (range 5-25 months, mean 13.3). CONCLUSION: Small cell carcinomas show the same histological patterns as their pulmonary counterpart. Immunohistochemistry reveals a wide spectrum of activity, enolase and keratins being the most constant. The present study confirms that the overall prognosis of this tumour is very poor.

Aged↗
PubMed1994

[Squamous cell carcinoma of the urinary bladder. Clinico-pathologic study of 7 cases].

A retrospective review of 552 patients with primary bladder cancer yielded 7 cases (1.2%) of pure squamous cell carcinoma. Their clinical presentations did not differ from conventional transitional cell carcinomas, gross hematuria being the most frequent complaint (6 cases). All the cases presented as flat tumors. They were large and frequently affected more than one topographic area. The trigone was almost always affected (6/7). Three cases were considered low and 4, high grade. There were no dysplastic changes on the peripheral mucosa in any case. At the time of diagnosis, all of them were deeply invasive (pT3 and pT4). Two cases were Stage III and 5 Stage IV, with involvement of lymph nodes and metastases to the lung (2 cases), liver (1 case), and bone (1 case). All the patients died of tumor and the overall survival was very poor (range 6-37 months; mean 17.4).

Aged↗
PubMed1993

The value of tumour spread, grading and growth pattern as morphological predictive parameters in bladder carcinoma. A critical revision of the 1987 TNM classification.

A group of 343 patients with bladder carcinomas was uniformly staged, both clinico-radiologically and pathologically. In accordance with pathological staging, they were treated from 1983 to 1990 and follow-up was closed on January 1992. No systemic chemotherapy regime was used. The present study was designed to assess the value of classical morphological parameters (tumour extension, histological subtype, grade and growth pattern) in the prediction of prognosis, and also to evaluate the adequacy of the current TNM classification (4th edition, 1987) of bladder cancer. The initial tumour stage appears the most useful criterion in the prediction of prognosis. Nevertheless, survival analysis confirms the necessity to modify the present TNM classification for routine clinical practice. In fact, stage III proves to be heterogeneous, and the difference in survival between categories pT3a and pT3b is even more statistically significant (log-rank P < 0.01) than the difference between pT2 and pT3 as a whole (log-rank P < 0.02). Consequently, invasion of the muscular layer should be reclassified into a common stage II, equivalent to the B category in the ABCD system. Moreover, stage IV is also heterogeneous in terms of survival. Despite the overall life-expectancy being rather poor for a patient with bladder carcinoma, three subsets with different prognosis (log-rank P < 0.001) can be identified: pT4N0M0; pTxN1-3M0; pTxNyM1, where x and y represent any number. Therefore, we believe that various subgroups should be distinguished in a future edition of the TNM classification. Current treatment modalities, involving the role of systemic chemotherapy and aimed at bladder preservation, make such innovations even more convenient for a new edition of the TNM classification of bladder cancer. Apart from tumour staging, several microscopic morphological parameters are valuable in distinguishing patients with different prognosis. Pure transitional-cell histology, papillar growth, and low grade, are favourable data. In fact, tumour grade, although somewhat subjective, is a factor of major prognostic importance. Pauwels' distinction of intermedium grade 2 into 2A and 2B is also helpful in the assessment of a population of "intermediate" prognosis. Similarly, with regard to superficial tumours, the division of infiltration levels of subepithelial connective tissue into "superficial" or "deep into the muscularis mucosae", is also relevant, even after stratification by grade.

Adenocarcinoma↗
PubMed1993

A case of Whipple's disease presenting as supraclavicular lymphadenopathy. A case report.

A case of Whipple's disease occurring in a 63-year-old woman is reported. Cervical lymphadenopathy and vague constitutional symptoms were soon followed by diarrhea and weight loss. Supraclavicular lymph node exeresis suggested the initial diagnosis, which was confirmed by intestinal biopsy. The concurrence of cystic spaces, PAS-positive foamy histiocytes and epithelioid granulomas is considered by the authors to provide a useful histological clue in the diagnosis of lymph node involvement in Whipple's disease. Pathologists must be aware of such an un-conventional presentation of this rare entity and therefore include it within the differential diagnosis of cervical and/or axillary lymphadenopathies.

Diagnosis, Differential↗
PubMed1993

[Bladder carcinoma: I. Epidemiologic considerations in the Basque country].

Review of several facts of epidemiological nature, from a study on bladder urothelial carcinoma cases detected over the period 1983-1990 in our centre, a reference hospital serving the Bilbao area. Certain data recently published by the Euskadi Cancer Register allowed us to establish some considerations related to the presence of this entity in our setting. Its incidence nears the highest rates in industrial countries. Age distribution, but no the men/female ratio, is similar to that in other settings. Overall, no difference was detected in sex-related survival. But, we corroborate that the youngest groups have the best prognosis. Also, an analysis is made of the association between age at diagnosis and several clinical and histopathological parameters.

Adolescent↗
PubMed1993

[Primary bladder carcinoma on diverticulum. Clinico-pathologic study of 5 cases].

This paper reviews our experience with the vesical cancer which develops on the diverticulum, a situation occurring in 1.5% of all vesical tumours in our setting. The condition's clinical features (diagnostic and therapeutic), usually detected in advanced stages, are emphasized. From a morphological point of view, histology of over half these tumours differs from the pure transitional one. There were two cases of pure transitional carcinoma, one small cells cancer, one squamous cells cancer and one with adenocarcinoma differentiating foci. Several sets of data, which include histological variability as well as presence of congenital diverticulum and urethral tumours, have led us to suspect the existence of morpho-genetical factors in the development of these neoplasias. However, the widely accepted carcinogenetic theory continues to be the most likely.

Aged↗
PubMed1993

[Inverted papillary carcinoma].

Some authors consider the papilloma to be a very low grade papillary carcinoma limited to the urothelium. Similarly, inverted papilloma can be interpreted to be a papillary carcinoma with an inverted growth pattern. Furthermore, the association of transitional cell carcinoma and inverted papilloma supports this concept. We investigated the frequency of transitional cell carcinoma associated with inverted growth--synchronous or metachronous--in our setting. Our results show that this association is present in 1.7% of the pure transitional cell carcinomas and in 2.6% of the superficial pure transitional cell carcinomas (pTa/pT1). We underscore the possibility of misinterpreting these lesions to be benign, while in fact they are potentially aggressive.

Carcinoma, Papillary↗
PubMed1986

Effect of the diabetic environment on the lipid metabolism of Ehrlich ascites cells.

One strain of Ehrlich ascites cells lacking of insulin receptors, was grown into control and diabetic mice and cells harvested from diabetic mice reimplanted into control mice. The fatty acid composition of neutral and polar lipids was analyzed and several parameters calculated. Results showed that it is possible to produce similar changes in the lipid fatty acid unsaturation of Ehrlich cells to those observed in the liver of the diabetic bearing mice. These changes may be reverted by growing these cells into control mice. The diabetic environment also promoted a relative increase in the radioactivity from incorporated in vitro into neutral lipids of Ehrlich cells. This metabolic adjustment, probably due to an induction of the enzyme diglyceride acyltransferase, was completely reverted by transplanting these cells in control mice. The metabolic adaptation of Ehrlich ascites cells to the diabetic environment did not modify their biological behaviour as pointed out by their mean generation time. The evidence presented here, showing relatively normal growth of Ehrlich cells in association with changes in the lipid fatty acid pattern and in lipid metabolism, indicates the adaptation of these cells, lacking of insulin receptors, to the environment provided by the diabetic mice.

Animals↗