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Biomedical subjects

I Rodriguez

Publications and source records attributed to I Rodriguez.

At least 55 records · Page 3Linked to original sources
PubMed1998

QT prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report.

BACKGROUND: The use of immunosuppressant agents is mandatory in the long-term management of transplant recipients. Herein, we report a case of near fatal cardiac arrhythmia related to the use of intravenous tacrolimus in a 35-year-old woman undergoing renal transplantation. METHODS: The patient had no previous history of cardiac disease, but an initial electrocardiogram demonstrated slightly prolonged QT and QTc intervals and normal sinus rhythm. Postsurgical immunosuppression included intravenous tacrolimus and methylprednisolone. During intravenous tacrolimus infusion, marked QT prolongation occurred. The patient suffered recurrent runs of torsade de pointes, refractory to aggressive medical management and requiring numerous defibrillations. Rapid atrial pacing eventually controlled the arrhythmia. RESULTS: We note not only a temporal association, but also a direct linear relationship, between this arrhythmia and blood tacrolimus levels. CONCLUSION: We believe this case presents a little recognized hazard associated with the use of intravenous tacrolimus and points to the need for careful predrug screening for QT prolongation. Tacrolimus has been shown to effect intracellular calcium and to prolong the action potential duration experimentally. This suggests that an increase in the intracellular calcium may underlie torsades de pointes associated with intravenous tacrolimus.

Adult↗
PubMed1998

Oxygen toxicity in mouse lung: pathways to cell death.

Mice exposed to 100% O2 die after 3 or 4 d with diffuse alveolar damage and alveolar edema. Extensive cell death is evident by electron microscopy in the alveolar septa, affecting both endothelial and epithelial cells. The damaged cells show features of both apoptosis (condensation and margination of chromatin) and necrosis (disruption of the plasma membrane). The electrophoretic pattern of lung DNA indicates both internucleosomal fragmentation, characteristic of apoptosis, and overall degradation, characteristic of necrosis. Hyperoxia induces a marked increase in RNA or protein levels of p53, bax, bcl-x, and Fas, which are known to be expressed in certain types of apoptosis. However, we did not detect an increased activity of proteases belonging to the apoptosis "executioner" machinery, such as CPP32 (caspase 3), ICE (caspase 1), or cathepsin D. Furthermore, administration of an ICE-like protease inhibitor did not significantly enhance the resistance to oxygen. Additionally, neither p53-deficient mice nor lpr mice (Fas null) manifested an increased resistance to hyperoxia-induced lung damage. These results show that both necrosis and apoptosis contribute to cell death during hyperoxia. Multiple apoptotic pathways seem to be involved in this, and an antiapoptotic strategy does not attenuate alveolar damage.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Prognosis in acute renal failure of septic origin: a multivariate analysis.

The goal of the present study was to identify variables associated with the outcome of patients with acute renal failure (ARF) of septic origin, using multivariate analysis. The records of 168 patients were reviewed retrospectively and a crude mortality of 74% was found. Both univariate as well as multivariate analysis demonstrated an association between mortality and variables which depended on patient related factors. These included age over 60 years and several underlying diseases such as pneumonia, peritonitis, and organ dysfunction. Only one variable (late oliguria) related to the ARF itself. Thus, outcome seems related to underlying disease more than to severity of ARF.

Acute Kidney Injury↗
PubMed1997

Control of compartmental affinity boundaries by hedgehog.

In Drosophila, each segmental primordium is subdivided into two cell populations, the anterior (A) and posterior (P) compartments by the selective activity of the transcription factor Engrailed (En) in P cells. Under En control, P cells secrete, but cannot respond to, the signalling protein Hedgehog (Hh). In contrast, and by default, A cells are programmed to respond to Hh by expressing other signalling molecules, such as Decapentaplegic (Dpp) and Wingless (Wg), which organize growth and patterning in both compartments. Cells of the A and P compartments do not intermix, apparently as a consequence of their having distinct cell affinities that cause them to maximize contact with cells of the same compartment, while minimizing contact with cells from the other compartment. This failure to mix has previously been ascribed to an autonomous and direct role for En in specifying a P, as opposed to an A, cell affinity. However, an alternative hypothesis is that Hh secreted by P cells induces A cells to acquire a distinct cell affinity, ensuring that a stable 'affinity boundary' forms wherever P and A cells meet. Here we show that the affinity boundary that segregates A and P cells into adjacent but immiscible cell populations is to a large extent a consequence of local Hh signalling, rather than a reflection of an intrinsic affinity difference between A and P cells.

Animals↗
PubMed1997

Conventional capillary electrophoresis in comparison with short-capillary capillary electrophoresis and microfabricated glass chip capillary electrophoresis for the analysis of fluorescein isothiocyanate anti-human immunoglobulin G.

Fast, efficient analysis of fluorescein isothiocyanate anti-human IgG was achieved in a short-capillary and in a microfabricated glass chip. The capillary was 6 cm long from injection end to detector with electric field strength of 0.268 kV/cm. Analyses were performed within 1 min. A glass microchip device was fabricated using standard photolithographic procedures and chemical wet etching. The channels were sealed using a direct bonding technique. For an effective length of 2.8 cm with electric field strength of 0.526 kV/cm, electrophoretic analysis was achieved in less than 16 s. Conventional capillary electrophoresis gave highly reproducible results and good detection limits. Analysis time was 2.5 min for a capillary with 47 cm effective length and electric field strength of 0.383 kV/cm.

Electrophoresis, Capillary↗
PubMed1997

An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis.

Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.

Animals↗
PubMed1997

Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation.

CD44 is a broadly distributed polymorphic glycoprotein that serves as the principal cell-surface receptor for hyaluronate. Although CD44-mediated cell interaction with hyaluronate has been implicated in a variety of physiologic events, including cell-cell and cell-substrate adhesion, cell migration, proliferation, and activation, as well as hyaluronate uptake and degradation, the biologic role of CD44 in vivo in various tissues remains to be determined. In the present work we have developed transgenic mice that express an antisense CD44 cDNA driven by the keratin-5 promoter. These mice lack detectable CD44 expression in skin keratinocytes and corneal epithelium and display abnormal hyaluronate accumulation in the superficial dermis and corneal stroma, distinct morphologic alterations of basal keratinocytes and cornea, and defective keratinocyte proliferation in response to mitogen and growth factors. These alterations are reflected by a decrease in skin elasticity, impaired local inflammatory response and tissue repair, delayed hair regrowth, and failure of the epidermis to undergo hyperplasia in response to carcinogen. Our observations indicate that two major functions of CD44 in skin are the regulation of keratinocyte proliferation in response to extracellular stimuli and the maintenance of local hyaluronate homeostasis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Mouse vaginal opening is an apoptosis-dependent process which can be prevented by the overexpression of Bcl2.

In the mouse, opening of the vaginal cavity to the skin is a late event, occurring around the fifth week of life; it can be induced in sexually immature mice by beta-estradiol injections. We have generated two lines of transgenic mice expressing the human Bcl2 protein in a variety of tissues. The vaginal cavity of the transgenic females remained permanently closed, a condition completely resistant to beta-estradiol injections; this was accompanied by a considerable distension of the genital tract. Histologic studies of vaginal sections at the time of opening to the skin in normal mice showed, by the TUNEL method which detects nuclei with fragmented DNA characteristic of apoptosis, that this event coincides with extensive apoptosis in the lower part of the vaginal mucosa, a process prevented in the bcl2 transgenic mice, which express Bcl2 in suprabasal epithelial cells and in subepithelial cells of the vaginal mucosa. In contrast, two lines of mice bearing a Bcl2 transgene placed under the control of a K10 keratin promoter, whose expression is restricted to the suprabasal layers of the epidermis, had a normal phenotype. Eyelids' formation and opening of the external ear canals, which also occur after birth in the mouse, were not altered in any of these transgenic lines; histological study of eye and ear sections at the time of these events failed to detect apoptosis. In conclusion, the tissue remodeling required to complete maturation of the mouse female genital tract at the time of puberty is an hormonally triggered apoptosis-dependent process.

Animals↗
PubMed1997

Bcl-2 prevents activation of CPP32 cysteine protease and cleavage of poly (ADP-ribose) polymerase and U1-70 kD proteins in staurosporine-mediated apoptosis.

Members of the the Bcl-2 and ICE/ced-3 gene families have been implicated as essential components in the control of the cell death pathway. Bcl-2 overexpression can prevent programmed cell death (PCD) in different cell types. ICE/ced-3-like proteases are synthesized as pro-enzymes and are activated by limited proteolysis. When overexpressed in diverse cell types, they trigger PCD. Bcl-2 can inhibit PCD mediated by these proteases, although as yet it is not clear at what specific step in the cell death pathway the protein acts. Here, we demonstrate that CPP32/Yama/Apopain, a member of the ICE/Ced-3 gene family, is processed during staurosporine-induced apoptosis in HeLa cells and that concomitant with CPP32 activation, two other proteins, poly (ADP-ribose) polymerase (PARP) and the U1-70 K small ribonucleoprotein, also undergo proteolysis. Overexpression of Bcl-2 prevents cleavage of CPP32, PARP and U1-70 K and protects HeLa cells from PCD. These results demonstrate that Bcl-2 controls PCD, by acting upstream of CPP32/Yama/Apopain.

Journal Article↗
PubMed1997

The cold pressor test: pharmacological and therapeutic aspects.

In this review article we discuss several aspects of the physiology, diagnosis, and pharmacology of the cold pressor test. The cold pressor test has been used for the diagnosis of cardiovascular reactivity in normotensive and hypertensive subjects. Some authors have stated that the cold pressor test will identify normotensive candidates at future risk of suffering from hypertensive disease. Interestingly, not all antihypertensive drugs block the exaggerated pressor response induced by cold stress. The most beneficial compounds belong to the alpha- and beta-blocker groups. Furthermore, several neurohormones such as norepinephrine, endothelins, prostaglandins, and angiotensin II have been reported to be released during cold exposure. The neurophysiology of cold pressor test indicates that after stress a great sympathetic discharge is induced at the spinal cord and terminal endings of the sympathetic nervous system. The release of norepinephrine is the cause of arteriolar vasoconstriction and elevation of blood pressure.

Antihypertensive Agents↗
PubMed1996

Control of neural precursor specification by proneural proteins in the CNS of Drosophila.

Formation of neural precursors in Drosophila is determined by proneural genes. The distinctive pattern of expression of some genes of the achaete-scute complex in the embryonic neuroectoderm has prompted the speculation that they could also function in the specification of neural precursor identity in the CNS. To test this hypothesis, we have analysed the capacity of different proneural proteins to promote the development of a particular CNS precursor, the MP2 precursor. Our results indicate that: (i) all known proneural proteins are similarly able to support the formation of a neural precursor at the position of MP2; (ii) different proneural proteins promote the expression of different characteristics of MP2; and (iii) a totally normal specification of the MP2 fate can only be attained by the proneural genes achaete or scute.

Animals↗
PubMed1996

Systemic injection of a tripeptide inhibits the intracellular activation of CPP32-like proteases in vivo and fully protects mice against Fas-mediated fulminant liver destruction and death.

Mice injected with anti-Fas antibody die within a few hours with total liver destruction due to massive apoptosis of hepatocytes. We show that this is preceded and accompanied by the sequential activation of cysteine proteases of the interleukin 1 beta-converting enzyme (ICE) and CPP32 types in the cytosol of the hepatocytes, and that proCPP32 cleavage and enzymatic activity can be prevented by intravenous injections of the tripeptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk), an inhibitor of ICE-like proteases. Four Z-VAD.fmk injections at 1-hour intervals abolished all signs of liver damage after anti-Fas antibody injection and resulted in 100% long-range recovery, without residual tissue damage, from a condition otherwise uniformly fatal within < 3 hours. This treatment was effective even when delayed until some liver DNA degradation was already detectable. Injections of the tetrapeptide Ac-YVAD.cmk, more specific for the ICE-like subfamily of cysteine proteases but less cell permeable, also gave protection, but at higher doses and when injections started before that of anti-Fas antibody. These observations afford a way of temporarily modulating a number of apoptotic processes in vivo and may have important therapeutic implications in some human diseases.

Amino Acid Chloromethyl Ketones↗
PubMed1996

A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection.

Stimulation of the Fas (APO-1, CD95) receptor, which is present on a variety of cells, usually triggers a process of programmed cell death. Systemic injection of anti-Fas antibody into mice leads to fulminant liver destruction resulting from massive hepatocyte apoptosis, and to rapid death. Hepatocytes bear Fas but do not express Bcl-2, a protein that plays, in a number of conditions, a protective role against apoptosis. We have generated mice whose liver expresses Bcl-2 as the result of bcl-2 transgene placed under the control of the hepatocyte-specific alpha1-anti-trypsin gene promoter, but is otherwise not distinguishable from that of normal mice. These mice display a marked to almost total resistance to liver damage induced by anti-Fas antibody injection. This protective effect of Bcl-2 occurs in the absence of significant variations, in the stimulated livers, in the level of expression of other proteins also involved in resistance or sensitivity to apoptosis, namely Bcl-x, Bax, Bad, Bak, and p53. Mice with protected livers, however, die almost as rapidly as normal mice, which indicates that acute lethality results from stimulation of Fas receptors present on other target organs or cells.

Animals↗
PubMed1996

Lack of transforming activity of fumonisin B1 in BALB/3T3 A31-1-1 mouse embryo cells.

The capacity of fumonisin B1 (FB1) to induce morphological transformation of cultured mammalian cells was assessed using BALB/3T3 A31-1-1 mouse embryo cells. FB1 with 90% purity was prepared from Fusarium proliferatum grown on whole corn. Cell growth was not inhibited by 48 hr of exposure at concentrations up to 1000 micrograms/ml. Moderate inhibition was induced by 6 days of exposure. In transformation assays with a 48-hr exposure, increases in transformed foci were observed at some concentrations; however, the responses were not reproducible. Prolonged exposure for up to 4 wk at 10, 100 and 500 micrograms/ml failed to induce increases in transformed foci. Analysis of combined results showed that only the increase induced by a 48-hr exposure at 500 micrograms/ml was significant. A trend test indicated the lack of a dose response for concentrations of 10-1000 micrograms/ml. FB1 seems to lack in vitro transforming activity.

Animals↗
PubMed1996

Plasma concentrations of vigabatrin in epileptic patients.

OBJECTIVE: To measure plasma concentrations of vigabatrin in a group of 30 adult epileptic patients with complex partial seizures (CPS) refractory to conventional antiepileptic drugs. With a view to better defining the drug's dose-response relationships in the presence of concomitant alternative antiepileptic drugs. METHODS: High-performance liquid chromatographic analysis of blood samples drawn at steady-state trough levels from patients receiving vigabatrin. RESULTS: The steady-state plasma concentrations of vigabatrin showed marked interpatient variability (CV = 59.5%). The mean concentration was 42 +/- 25 micrograms/ml (range 11.5-102.7 micrograms/ml). Nineteen patients (63%) had plasma levels between 20 and 60 micrograms/ml. The plasma clearance of vigabatrin ranged from 0.24 to 1.37 ml/min/kg (mean +/- SD = 0.74 +/- 0.40 ml/min/kg), with a median value of 0.64 ml/min/kg. Concomitant treatment with carbamazepine increased the plasma clearance of vigabatrin from 0.59 ml/min/kg (monotherapy), 0.54 ml/min/kg (co-treated with phenobarbital) and 0.41 ml/min/kg (co-treated with valproic acid) to 0.92 ml/min/kg. CONCLUSION: Vigabatrin plasma levels show wide interpatient variability, and co-administration with carbamazepine increases vigabatrin's clearance. While there is no relationship between plasma level and anti-epileptic effect, abnormally high levels of the drug may increase toxicity.

Adult↗
PubMed1996

A mechanism of restricted human immunodeficiency virus type 1 expression in human glial cells.

We characterized in detail the life cycle of human immunodeficiency virus type 1 (HIV-1) in human glioma H4/CD4 cells which stably express transfected CD4 DNA (B. Volsky, K. Sakai, M. Reddy, and D. J. Volsky, Virology 186:303-308, 1992). Infection of cloned H4/CD4 cells with the N1T strain of cell-free HIV-1 (HIV-1/N1T) was rapid and highly productive as measured by the initial expression of viral DNA, RNA, and protein, but all viral products declined to low levels by 14 days after infection. Chronically infected, virus-producing H4/CD4 cells could be obtained by cell cloning, indicating that HIV-1 DNA can integrate and remain expressed in these cells. The HIV-1 produced in H4/CD4 cells was noninfectious to glial cells, but it could be transmitted with low efficiency to CEM cells. Examination of viral protein composition by immunoprecipitation with AIDS serum or anti-gp120 antibody revealed that HIV-1/N1T-infected H4/CD4 cells produced all major viral proteins including gp160, but not gp120. Deglycosylation experiments with three different glycosidases determined that the absence of gp120 was not due to aberrant glycosylation of gp160, indicating a defect in gp160 proteolytic processing. Similar results were obtained in acutely and chronically infected H4/CD4 cells. To determine the generality of this HIV-1 replication phenotype in H4/CD4 cells, nine different viral clones were tested for replication in H4/CD4 cells by transfection. Eight were transiently productive like N1T, but one clone, NL4-3, established a long-lived productive infection in H4/CD4 cells, produced infectious progeny virus, and produced both gp160 and gp120. We conclude that for most HIV-1 strains tested, HIV-1 infection of H4/CD4 is restricted to a single cycle because of the defective processing of gp160, resulting in the absence of gp120 on progeny virus.

Binding Sites↗