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Biomedical subjects

P Sanchez

Publications and source records attributed to P Sanchez.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prostate brachytherapy--the community hospital experience.

One of the options for treating localized carcinoma of the prostate includes the implantation of radioactive seeds under ultrasound guidance (brachytherapy). A community hospital-based prostate brachytherapy program was started in 1992. The overall survival and disease-free survival figures for the initial 100 patients treated in this program seem comparable to patients treated by radical prostatectomy or brachytherapy in larger series. The main side effects of brachytherapy included nocturia, daytime urinary frequency, dysuria, and proctitis. These side effects were transient and decreased to less than 10% by 12 to 24 months following implantation. Prostate brachytherapy can be effectively and safely provided in a community hospital setting.

Adenocarcinoma↗
PubMed1999

The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation.

The two members of the atypical protein kinase C (aPKC) subfamily of isozymes (zetaPKC and lambda/iotaPKC) are involved in the control of nuclear factor kappaB (NF-kappaB) through IKKbeta activation. Here we show that the previously described aPKC-binding protein, p62, selectively interacts with RIP but not with TRAF2 in vitro and in vivo. p62 bridges the aPKCs to RIP, whereas the aPKCs link IKKbeta to p62. In this way, a signaling cascade of interactions is established from the TNF-R1 involving TRADD/RIP/p62/aPKCs/IKKbeta. These observations define a novel pathway for the activation of NF-kappaB involving the aPKCs and p62. Consistent with this model, the expression of a dominant-negative mutant lambda/iotaPKC impairs RIP-stimulated NF-kappaB activation. In addition, the expression of either an N-terminal aPKC-binding domain of p62, or its C-terminal RIP-binding region are sufficient to block NF-kappaB activation. Furthermore, transfection of an antisense construct of p62 severely abrogates NF-kappaB activation. Together, these results demonstrate that the interaction of p62 with RIP serves to link the atypical PKCs to the activation of NF-kappaB by the TNFalpha signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Echocardiographic evaluation in patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

Cardiovascular abnormalities have been considered important extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD). However, little is known about their prevalence in patients with ADPKD undergoing hemodialysis (HD). To investigate whether cardiac abnormalities are more prevalent in these patients, clinical and echocardiographic manifestations of cardiovascular disease were evaluated in a group of 32 patients with ADPKD and a matched control group of 32 patients without diabetes treated by chronic HD for more than 6 months. Predialysis systolic and diastolic blood pressure (BP), prevalence of hypertension, and number of patients requiring antihypertensive medications were lower in the ADPKD group than controls. There was no difference in the prevalence of cardiac events, including cardiac failure, ischemic heart disease, and arrhythmia. Systolic dysfunction, diastolic patterns, and left ventricular hypertrophy were similar in the two groups. In patients with ADPKD, simple regression analysis showed left ventricular mass (LVM) index was correlated with hemoglobin level and predialytic systolic and diastolic BPs. In multiple regression analysis, predialysis systolic BP was the only independent variable linked to LVM index. The prevalence of aortic, mitral, and tricuspid valve disease did not differ between groups. In conclusion, the occurrence of cardiovascular complications in patients with ADPKD is similar to that of HD patients with other primary renal diseases, although hypertension is less prevalent.

Aged↗
PubMed1999

Effect of ATP depletion on the palmitoylation of myelin proteolipid protein in young and adult rats.

The present study was designed to determine whether the palmitoylation of the hydrophobic myelin proteolipid protein (PLP) is dependent on cellular energy. To this end, brain slices from 20- and 60-day-old rats were incubated with [3H]palmitate for 1 h in the presence or absence of various metabolic poisons. In adult rats, the inhibition of mitochondrial ATP production with KCN (5 mM), oligomycin (10 microM), or rotenone (10 microM) reduced the incorporation of [3H]palmitate into fatty acyl-CoA and glycerolipids by 50-60%, whereas the labeling of PLP was unaltered. Incubation in the presence of rotenone (10 microM) plus NaF (5 mM) abolished the synthesis of acyl-CoA and lipid palmitoylation, but the incorporation of [3H]palmitate into PLP was still not different from that in controls. In rapidly myelinating animals, the inhibition of both mitochondrial electron transport and glycolysis obliterated the palmitoylation of lipids but reduced that of PLP by only 40%. PLP acylation was reduced to a similar extent when slices were incubated for up to 3 h, indicating that exogenously added palmitate is incorporated into PLP by ATP-dependent and ATP-independent mechanisms. Determination of the number of PLP molecules modified by each of these reactions during development suggests that the ATP-dependent process is important during the formation and/or compaction of the myelin sheath, whereas the ATP-independent mechanism is likely to play a role in myelin maintenance, perhaps by participating in the periodic repair of thioester linkages between the fatty acids and the protein.

Acylation↗
PubMed1998

Time-course effects of human recombinant luteinizing hormone on porcine Leydig cell specific differentiated functions.

Since recombinant hormones are considered as safer and more reliable in their bioactivity than extractive hormones, the recently available human recombinant luteinizing hormone (r-hLH), will probably replace hCG in the near future, for clinical purposes. This prompted us to investigate whether or not, and by which mechanisms, r-hLH can induce a desensitization of signal transduction and/or an up-regulation of steroidogenic capacity in Leydig cells. The effects of a 30 min to 24 h exposure to r-hLH (10(-9) M) on the differentiated functions of cultured immature porcine Leydig cells were studied by measuring the following parameters: LH/hCG receptor number and mRNA, hCG-, cholera toxin- and forskolin-induced cAMP production, G protein alphas subunit content of the membrane, hCG-, cholera toxin-, forskolin-, 8Br-cAMP-, 22R-OH-cholesterol-, progesterone-, 170H-progesterone-, DHEA-, delta4-androstenedione-induced testosterone secretion and StAR, 3beta-HSD, cytochrome P-450scc and P-450c17 mRNAs. hCG binding sites and LH/hCG receptor mRNA were slowly down regulated by r-hLH, reaching 47+/-1 and 18+/-7% of control at 24 h, respectively. Down-regulation of both hCG- and cholera toxin-induced cAMP production occurred earlier and was more marked, and at 24 h represented only 2.7+/-0.5 and 12.5+/-3.6% of control. Due to the synergistic effect of r-hLH and forskolin on cAMP production, the forskolin-induced cAMP was higher in r-hLH treated than in control cells, but this response also declines with time and was, at 24 h, only 32% of that observed at 30 min. This decreased cAMP production was associated with a less marked decline in the amount of membrane content of Galphas protein. The testosterone production in response to hCG, cholera toxin, forskolin and 8Br-cAMP declined to reach a nadir at 6 h but increased thereafter and at 24 h was significantly higher than in control cells. In contrast, the conversion of several precursors into testosterone remained stable or increased slightly during the first hours of r-hLH treatment and significantly increased at 24 h and this was associated with an increase of StAR, 3beta-HSD, P-450scc and P-450c17 mRNAs. Taken together, the present results indicate that, despite the marked down-regulation of transmembrane signaling, r-hLH increased the steroidogenic capacity of Leydig cells by increasing the expression of several genes encoding the proteins involved in testosterone synthesis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

[Asthmatic crisis and spontaneous rupture of the esophagus].

We report a case of spontaneous rupture of oesophagus revealed by a severe asthma attack, in a 78-year-old woman, with continuous dyspneic asthma treated with corticosteroids. We discuss the diagnostic difficulties in spontaneous oesophageal rupture, and emphasize the necessity for always looking for a triggering factor in case of severe attacks of asthma not responding to treatment.

Aged↗
PubMed1998

Enhancement of long-term testosterone secretion and steroidogenic enzyme expression in human Leydig cells by co-culture with human Sertoli cell-enriched preparations.

We have shown previously that long-term testosterone secretion, which decreases when human Leydig cells are cultured alone, increases when purified human Leydig and Sertoli cells are cultured together. In this work, human Leydig cell functions were studied further during in vitro culture, either alone or with human Sertoli cells, on a basal membrane derived from bovine corneal endothelial cells. The secretion of testosterone increased during the first week of co-culture and remained elevated up to day 12 of culture. In one prolonged co-culture, testosterone secretion decreased progressively after day 12 and, after 1 month of culture, was at a level similar to that observed during the first 48 h. After culture for 48 h, testosterone secretion in the co-culture was enhanced by 162 +/- 5% (p < 0.0001) compared with values observed when Leydig cells were cultured alone (42.6 +/- 10.6 ng/10(6) Leydig cells/48 h; mean +/- SEM). This change was associated with increase in mRNA levels for 3 beta-hydroxysteroid dehydrogenase delta 5-delta 4-isomerase (2.49 +/- 0.58-fold), cytochrome P450c17 (2.81 +/- 0.99-fold), cytochrome P450scc (5.20 +/- 0.13-fold) and cytochrome P450 aromatase (1.73 +/- 0.21-fold) when Leydig cells were co-cultured with Sertoli cells (p < 0.05 for each enzyme). IGF-I mRNA levels were higher (2.77 +/- 0.72-fold for 7.6 kb and 1.41 +/- 0.07-fold for 1.1-1.3 kb transcripts) in the Leydig-Sertoli cell co-cultures than the sum of the levels in Leydig and in Sertoli cells cultured alone. Both basal and hCG-induced testosterone secretion were enhanced by treatment of the co-culture with human recombinant FSH (50 mIU/mL). For basal testosterone secretion, this increase amounted to 163 +/- 5% compared with Leydig cells cultured alone (p < 0.0001) and by 112 +/- 4% compared with non-FSH treated co-cultures (p < 0.01); for hCG-stimulated testosterone secretion this increase was 220 +/- 12% compared with Leydig cells cultured alone (p < 0.0001) and 132 +/- 8% compared with non-FSH treated co-cultures (p < 0.01). This study confirms the enhancement of long-term testosterone secretion by adult human Leydig cells by co-culture with adult human Sertoli cells and shows that this effect is associated with an enhancement of the expression of several steroidogenic enzymes; it might be mediated, as in other species, through increased production of IGF-I by co-culture.

Adult↗
PubMed1998

Veratridine-induced depolarization reduces the palmitoylation of brain and myelin glycerolipids.

In this study, we have investigated the effect of neuronal depolarization on the palmitoylation of myelin lipids. For this purpose, brain slices from 60-day-old rats were incubated with [3H]palmitate for 1 h in the presence or absence of various drugs. Veratridine (100 microM) reduced the incorporation of [3H]palmitate into all brain glycerolipids by 40-50%, whereas the labeling of sphingolipids was unaffected. Similar results were obtained by using [3H]glycerol as a precursor, demonstrating that veratridine also causes a reduction in the de novo synthesis of glycerolipids. Both tetrodotoxin (1 microM) and ouabain (1 mM) prevented the effect of veratridine, indicating that it is mediated through the opening of voltage-gated sodium channels and involves the stimulation of the Na+/ K+ pump. Decreased levels of both ATP, due to activation of the Na+,K+-ATPase, and the precursor palmitoyl-CoA were found in the veratridine-treated slices, thus explaining the reduction in lipid synthesis. Neuronal depolarization also decreased the synthesis of lipids present in the myelin fraction. The relatively high specific radioactivity of myelin lipids and the results from both repeated purification experiments and mixing experiments ruled out the possibility that the radioactive lipids present in myelin could derive from contamination with other subcellular fraction(s). Because neither mature oligodendrocytes nor myelin is known to express voltage-dependent Na+ channels, it is conceivable that the effect of veratridine on myelin glycerolipid metabolism occurs by an indirect mechanism such as an increase in the extracellular [K+]. However, the presence of 60 mM KCl in the medium did not affect the acylation of either brain or myelin lipids. These results raise questions as to the absence of sodium channels in myelinating oligodendrocytes and/or myelin.

Adenosine Triphosphate↗
PubMed1998

Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62.

An increasing number of independent studies indicate that the atypical protein kinase C (PKC) isoforms (aPKCs) are critically involved in the control of cell proliferation and survival. The aPKCs are targets of important lipid mediators such as ceramide and the products of the PI 3-kinase. In addition, the aPKCs have been shown to interact with Ras and with two novel proteins, LIP (lambda-interacting protein; a selective activator of lambda/iotaPKC) and the product of par-4 (a gene induced during apoptosis), which is an inhibitor of both lambda/iotaPKC and zetaPKC. LIP and Par-4 interact with the zinc finger domain of the aPKCs where the lipid mediators have been shown to bind. Here we report the identification of p62, a previously described phosphotyrosine-independent p56(lck) SH2-interacting protein, as a molecule that interacts potently with the V1 domain of lambda/iotaPKC and, albeit with lower affinity, with zetaPKC. We also show in this study that ectopically expressed p62 colocalizes perfectly with both lambda/iotaPKC and zetaPKC. Interestingly, the endogenous p62, like the ectopically expressed protein, displays a punctate vesicular pattern and clearly colocalizes with endogenous lambda/iotaPKC and endogenous zetaPKC. P62 colocalizes with Rab7 and partially with lamp-1 and limp-II as well as with the epidermal growth factor (EGF) receptor in activated cells, but not with Rab5 or the transferrin receptor. Of functional relevance, expression of dominant negative lambda/iotaPKC, but not of the wild-type enzyme, severely impairs the endocytic membrane transport of the EGF receptor with no effect on the transferrin receptor. These findings strongly suggest that the aPKCs are anchored by p62 in the lysosome-targeted endosomal compartment, which seems critical for the control of the growth factor receptor trafficking. This is particularly relevant in light of the role played by the aPKCs in mitogenic cell signaling events.

Adaptor Proteins, Signal Transducing↗
PubMed1997

T cell tolerance to kappa light chain (L kappa): identification of a naturally processed self-C kappa-peptidic region by specific CD4+ T cell hybridomas obtained in L kappa-deficient mice.

In contrast to H-2d kappa light chain-deficient mice (kappa-/-), BALB/c (kappa+/+) mice fail to respond to kappa light chains (L kappa). This suggests that C kappa-specific T cells are tolerant to this self-antigen in kappa+/+ mice. To get insights into the cellular and molecular basis of this tolerance, we first characterized the presented L kappa-derived C kappa-peptidic region(s). Among a library of overlapping peptides spanning the whole C kappa sequence, only three consecutive peptides are recognized by CD4+ T cell hybridomas obtained in L kappa-immunized kappa-/- mice. This C kappa-peptidic region, which is also the only one containing the I-Ed-binding consensus motif, is immunogenic since it is able to prime lymph node cells of kappa-/- mice to subsequent in vitro proliferative response to either L kappa or kappa+/+ APC. Conversely, no kappa+/+ T cell proliferation is observed under the same conditions. Activation of our hybridomas by cells from central and peripheral lymphoid tissues reveals that this C kappa region is naturally expressed on BALB/c kappa+/+ APC. In addition to B cells, macrophages and dendritic cells are able to present this region. Taken together our data suggest that the described self-C kappa region is implicated in the C kappa-specific CD4+ T cell tolerization in BALB/c mice.

Amino Acid Sequence↗
PubMed1997

[Physiopathology of closed thoracic trauma].

Any thoracic trauma causes more or less severe hypoxia, due to pain, pleural effusion, mechanical ventilation disorders and pulmonary contusion. These four factors lead to bronchial congestion, which in turn aggravates hypoxia. More or less rapidly a vicious circle of respiratory failure is created. It can be broken only by early treatment of the cause. Without such treatment, respiratory failure quickly becomes autonomic and treatment of the cause is no longer sufficient.

Adult↗
PubMed1997

Does positive selection determine the B cell repertoire?

To know whether each newly formed B cell has an equal chance of survival in the organism, we analyzed the composition of the B cell repertoire of extremely limited diversity by generating mu-transgenic kappa-knockout mice. Surprisingly, in both types of mice studied, the B cell repertoire is mainly composed of cells expressing the mu-transgene-encoded chain associated with only one out four available lambda types depending on the mu transgene. Moreover, B cell differentiation cultures in vitro show that newly formed B cells can express the various lambda types regardless of the presence or absence of the mu transgenes. These results show a drastic impact of the heavy chain on the lambda light chain repertoire expressed in the periphery. The overexpression of a unique heavy/light chain pairing therefore results from selective processes. The immature B cells may be positively selected to provide the immunocompetent B cells in the periphery.

Animals↗
PubMed1997

Syphilis serology in human immunodeficiency virus infection: evidence for false-negative fluorescent treponemal testing.

Injection drug users were assessed serologically for human immunodeficiency virus infection and syphilis every 6 months. Treatment histories were reviewed for any high-titer biologic false-positive (BFP) reactors, that is, persons with rapid plasma reagin (RPR) titers > or = 1:4 and negative results for fluorescent treponemal antibody absorption (FTA-ABS) tests. Selected sera were analyzed further by immunoblotting for the presence of antibodies reactive with specific Treponema pallidum antigens. Of 112 BFP reactors, 35 (31%) had at least one RPR test reactive at a dilution >1:8 while the FTA-ABS test remained nonreactive. Five reactors (4.5%) converted from nonreactive to reactive by FTA-ABS test; 4 (3.6%) were reactive by FTA-ABS tests but later became nonreactive. Antibodies to T. pallidum membrane antigens were detected in some samples that were persistently nonreactive by FTA-ABS test. Serologic patterns over time, along with very high-titer BFP reactions and reactivity with T. pallidum-specific antigens, suggest that some BFP reactions may represent FTA-negative syphilis.

Antibodies, Bacterial↗
PubMed1997

Stimulating effect of both human recombinant inhibin A and activin A on immature porcine Leydig cell functions in vitro.

In addition to the regulation of FSH secretion, it has been clearly shown that inhibin and activin have paracrine/autocrine effects in the gonads. We have studied the effect of human recombinant inhibin A and human recombinant activin A on immature porcine Leydig cells in vitro. Leydig cells were prepared by collagenase digestion of testes from 3-week-old piglets, purified on Percoll gradient, then cultured in a chemically defined medium. The cells were treated with increasing amounts of inhibin A or activin A (0.5-200 ng/ml). Direct application of either inhibin A or activin A on Leydig cells for 4 or 48 h did not stimulate basal testosterone secretion. Conversely, treatment of the cells for 48 h with either factor resulted in a dose-dependent increase in hCG-stimulated testosterone secretion (10[-9] M hCG, 2 h) with a maximal effect of 2.40 +/- 0.37- and 2.43 +/- 0.37-fold increases for inhibin A and activin A, respectively, and these changes were associated with a slight increase in LH/hCG-binding sites (1.37 +/- 0.19- and 1.24 +/- 0.11-fold increases). In addition, both inhibin A and activin A enhanced messenger RNA (mRNA) levels of LH/hCG receptor (2.75 +/- 0.40- and 2.53 +/- 0.60-fold increases) and cytochrome P450 17alpha-hydroxylase (6 +/- 1- and 3.5 +/- 0.6-fold increases), but had no effect on side-chain cleavage cytochrome P450 or cytochrome P450 aromatase mRNAs. 3beta-Hydroxysteroid dehydrogenase mRNA levels were increased (3.1 +/- 1.3-fold increase) by activin A, but not by inhibin A. However, inhibin A blocked the stimulatory action of activin A. In keeping with these changes in the steroidogenic enzyme mRNAs, both peptides enhanced the conversion of exogenous 22R-hydroxycholesterol and progesterone, but only activin A increased the conversion of dehydroepiandrosterone into testosterone. In conclusion, our findings demonstrate that both inhibin A and activin A have a stimulatory effect on immature porcine Leydig cell differentiated function in vitro. As inhibin has a stimulatory and activin has an inhibitory effect on rat Leydig cell function in vitro, the effects of these factors on Leydig cells seem to be species dependent.

Activins↗
PubMed1997

Today's CIO: catalyst for managed care change.

As the impact of managed care increases and capitation becomes all pervasive, healthcare providers' attention to cost control will intensify. For integrated delivery networks (IDNs) to be competitive, today's CIO must leverage managed care as a catalyst for change, and use a sophisticated information system toolset as the means to an integrated end. An area many CIOs target for fast results and maximum cost savings in resource management. This article reviews how Dick Escue, chief information officer at Baptist Memorial Health Care Corporation (Memphis, TN), uses electronic information management systems to integrate and conserve the resources of Baptist's widespread healthcare organization.

Administrative Personnel↗
PubMed1996

The product of par-4, a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C.

The atypical PKCs are involved in a number of important cellular functions, including cell proliferation. We report here that the product of the par-4 gene specifically interacts with the regulatory domains of zeta PKC and lambda/LPKC, which dramatically inhibits their enzymatic activity. This is particularly challenging, because expression of par-4 has been shown to correlate with growth inhibition and apoptosis. Results are shown here demonstrating that the expression of par-4 in NIH-3T3 cells induces morphological changes typical of apoptosis, which are abrogated by cotransfection of either wild-type zeta PKC or lambda/LPKC, but not by their respective kinase-inactive mutants. These findings support a role for the atypical PKC subspecies in the control of cell growth and survival.

3T3 Cells↗