PubMed Health⌕ Search

Biomedical subjects

M Prieto

Publications and source records attributed to M Prieto.

At least 73 records · Page 4Linked to original sources
PubMed1999

Tangential migration of young neurons arising from the subventricular zone of adult rats is impaired by surgical lesions passing through their natural migratory pathway.

In the brain of adult rodents, young neurons arising from the subventricular zone (SVZ) of the lateral ventricle migrate tangentially along the rostral migratory stream (RMS) toward the olfactory bulb. The aim of this study was to determine whether surgical lesions placed through the RMS could affect the rostral migration of these newly formed neurons. Confocal and electron microscopy were used to characterize their anatomical organization within the intact and lesioned forebrains. As soon as 7 days and up to 45 days after placing a surgical lesion through the proximal portions of the RMS, numerous cells immunostained for polysialylated neural cell adhesion molecule (PSA-NCAM) were detected both (1) throughout the lesional cavity extending from the cortex to the anterior commissura, and (2) within the tissue located caudal to the lesion. In both regions, these PSA-NCAM-immunostained cells were labeled for neuronal markers but were negative for glial fibrillary acidic protein (GFAP). After administration of the proliferation marker bromodeoxyuridine (BrdU), nuclear labeling was associated with cells immunostained for PSA-NCAM but GFAP-negative, that accumulated within the lesional cavity and in the tissue caudal to the lesion. For the longest postlesional delays, a number of the PSA-NCAM-immunostained neurons located in various portions of the lesional cavity exhibited intense immunostaining for gamma-aminobutyric acid, whereas only a few of them exhibited faint immunostaining for tyrosine hydroxylase. These data indicate that surgical lesions placed through the RMS of adult rats impede the migration toward the olfactory bulb of the neuroblasts arising from the SVZ, inducing their accumulation and their partial differentiation in forebrain regions caudal to the lesion.

Animals↗
PubMed1999

High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes.

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporine-based HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNA-positive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporine-based immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P =.02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P =.001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P =.008 and.18, respectively). In conclusion, HCV genotype 1b-infected liver recipients are at a high risk of developing graft cirrhosis in the first 4 to 5 years following transplantation, especially those with previous rejection episodes. First-year liver biopsies may help to sooner identify patients at the highest risk, improving further patient management.

Adult↗
PubMed1999

Progression of cardiomyopathy and neuropathy after liver transplantation in a patient with familial amyloidotic polyneuropathy caused by tyrosine-77 transthyretin variant.

Familial amyloidotic polyneuropathy is an inherited form of amyloidosis associated with a mutant form of a protein called transthyretin. The Methionine-30 variant is the most frequent mutation observed. This disorder is caused by deposition of this protein as amyloid in several organs, such as the heart, kidneys, and peripheral nervous system. The disease is always progressive and fatal, and patients die 7 to 10 years after the onset of symptoms. Liver transplantation is at present the only choice for these patients because it provides improvement of symptoms and/or stops progression of the disease in most patients. We report the case of a patient who showed clear progression of cardiomyopathy and neuropathy after liver transplantation.

Amyloid Neuropathies↗
PubMed1999

Differential sensitivity of cultured tanycytes and astrocytes to hydrogen peroxide toxicity.

Tanycytes present in the mediobasal hypothalamus are able to support axonal regeneration and neuron survival. Pilot experiments of transplantation of these cells into various lesioned areas of the central nervous system (CNS) were thus performed to determine whether these cells could support the regeneration of the lesioned axons. These pilot experiments, however, demonstrated that the grafted tanycytes failed to survive in the lesioned sites. The present study was designed to determine which of the compounds released at the lesion would be toxic for tanycytes. Tanycyte cultures obtained from the median eminence of 10-day-old rats and astrocyte cultures obtained from the cortex of 10-day-old rats or E-14 embryos were incubated with two types of toxic molecules, including excitatory amino acids (EAA) and hydrogen peroxide (H2O2). The effect of these substances on cell death was estimated by measuring the lactate deshydrogenase (LDH) released and the surface occupied by immunostained glial structures after each treatment. The results indicated that the viability of both the tanycytes and the astrocytes was not affected by incubation for 24 h with 1 mM glutamate or 1 mM kainate. In contrast, increasing concentrations of H2O2 induced concentration-dependent cell death of tanycytes and immature astrocytes, without affecting the mature astrocytes. The use of antioxidant molecules such as catalase, tempol, or vitamin C effectively protected cultured tanycytes from H2O2 toxicity. These data indicate that (1) both mature astrocytes and tanycytes are resistant to EAA and (2) contrary to mature astrocytes, immature astrocytes and tanycytes are sensitive to the free radicals generated by H2O2. This suggest that oxidative stress is at least partly responsible for the death of tanycytes grafted into the lesioned CNS.

Animals↗
PubMed1999

A possible attenuation of stress-induced increases in striatal dopamine metabolism by the expression of non-functional masticatory activity in the rat.

It is thought that the expression of oral parafunctions may provide an outlet for stress or aggressiveness in man. Stress-induced increases in central noradrenergic neurotransmission are attenuated in rats which are allowed to bite during stress. Striatal dopaminergic neurotransmission is involved in the genesis of parafunctional oral movements in rodents. As tail pinch is the stressor which most clearly provokes non-functional masticatory activity (NFMA), and also increases striatal dopamine (DA) activity in rats, we investigated whether the expression of NFMA during tail pinch could modify the changes in striatal dopaminergic neurotransmission induced by this stressor. Rats were subjected to tail pinch for 5 min, and the duration of the NFMA displayed was recorded. As an index of dopaminergic activity, 3,4-dihydroxyphenylalanine (DOPA) accumulation and DA and 3,4-dihydroxyphenylacetic (DOPAC) contents in both striata were determined by high-performance liquid chromatography. Striatal DOPA accumulation was similarly increased in relation to control, both in rats which did and did not display NFMA during tail pinch. However, the increases in striatal DOPAC contents, reported 24 min after the stress session, were lower in animals which had displayed NFMA. These results provide further evidence in support of the assumption that the expression of parafunctional masticatory activity attenuates the effects of stress on central catecholaminergic neurotransmission.

Analysis of Variance↗
PubMed1999

The importance of a tumor capsule in columnar cell thyroid carcinoma: a report of two cases and review of the literature.

Two cases of papillary columnar cell thyroid carcinoma are presented. A 49-year-old man presented with lymph node and pulmonary metastases at diagnosis; a 51-year-old woman developed local recurrence and lung and bone metastases 3 years postsurgery. Death occurred after 52 and 57 months, respectively. The first case lacked a tumor capsule, although the second exhibited capsule remains with extensive tumor cell infiltration. A review is made of all similar cases reported to date in the literature, placing emphasis on the epidemiological and prognostic differences observed in terms of circumscribed or noncircumscribed tumor. The presence of a capsule was associated with a higher frequency of female patients and a favorable prognosis. In contrast, tumors profusely infiltrating the thyroid parenchyma or extrathyroid tissues in the absence of a capsule, found in similar proportion of men and women had a fatal prognosis.

Carcinoma, Papillary↗
PubMed1999

Occlusal disharmonies modulate central catecholaminergic activity in the rat.

Occlusal disharmonies have classically been thought to be involved in the etiopathogenesis of bruxism, as have, more recently, alterations in central neurotransmission, particularly dopaminergic neurotransmission. However, the connection between these two factors has still not been established. In this study, we assessed the effects of diverse occlusal disharmonies, maintained for either 1 day or 14 days, on neurochemical indices of dopaminergic and noradrenergic activity in the striatum, frontal cortex, and hypothalamus of the rat. The in vivo activity of tyrosine hydroxylase, determined as the accumulation of 3,4-dihydroxyphenylalanine (DOPA), 30 min after the administration of 3-hydroxybenzylhydrazine, a DOPA decarboxylase inhibitor, and dopamine and noradrenaline contents were quantified by high-performance liquid chromatography with electrochemical detection. The wearing of an acrylic cap on both lower incisors for 1 day induced a significant increase in DOPA accumulation in the regions analyzed, with parallel increases in dopamine levels in the hypothalamus and dopamine and noradrenaline in the frontal cortex. After the cap was maintained for 14 days, DOPA accumulation tended to return to control values, except in the left striatum, thereby causing an imbalance between hemispheres. In contrast, 1 or 14 days after the lower left and the upper right incisors were cut, less pronounced changes in catecholaminergic neurotransmission were found in the brain areas studied. Moreover, the cutting of one lower incisor did not modify either DOPA accumulation or dopamine and noradrenaline contents in the striatum or hypothalamus. These results provide experimental evidence of a modulation of central catecholaminergic neurotransmission by occlusal disharmonies, being dependent on the nature of the incisal alteration and on the time during which it was maintained.

Analysis of Variance↗
PubMed1999

Bacterial microflora of wild brown trout (Salmo trutta), wild pike (Esox lucius), and aquacultured rainbow trout (Oncorhynchus mykiss).

Initial numbers of bacteria associated with wild (brown trout and pike) and cultured (rainbow trout) freshwater fish as well as with the water in which they were caught were determined. Subsequently, a total of 979 randomly selected isolates were characterized and identified to the genus level. For all counts performed (aerobes, psychrotrophs, anaerobes, Enterobacteriaceae, and enterococci), no significant differences were observed in water samples, the highest level corresponding to psychrotrophs in pike environments (4.23 X 10(3) CFU/ml). Overall, the skin and intestinal content of brown trout were the most contaminated, while rainbow trout specimens (gills and gut) yielded the lowest numbers. For all bacterial groups, pike gills had the highest numbers. Counts for all of the sampling sites compare well with findings in other temperate geographical environments. Biological characteristics (feeding and skin properties) and the use of antimicrobials in aquaculture might have influenced these results. Motile and nonmotile aerobic gram-negative bacteria together with Enterobacteriaceae accounted for 50 to 70% of the psychrotrophs isolated from water. Micrococcaceae, lactic acid bacteria, Bacillus, and coryneforms were also found. The groups represented in psychrotrophic isolates from the outer surfaces do not reflected those detected in water, so it was common that those organisms recovered in significant numbers from fish were not detected in surrounding habitat of the fish. Motile aeromonads and Carnobacterium were the dominant psychrotrophs in the guts of pike and brown trout, respectively. The intestinal content of reared fish gave a high incidence of Bacillus and coryneforms, while Enterobacteriaceae was absent. Again, rearing practices could have influenced this finding. Listeria monocytogenes was not detected in any of the examined samples. Two strains of Salmonella, which belonged to the same serovar and lysotype, were recovered from pond-water samples taken from one facility on different sampling days. From the gut of a pike specimen and from the pike's environment, two Plesiomonas shigelloides strains of different serovars were recovered. These latter four strains were resistant to a considerable number of antimicrobial compounds (multiple antibiotic resistance indices > 0.2).

Animals↗
PubMed1999

Comparative analysis of quantification of viral load in patients infected with hepatitis C virus: quantiplex HCV RNA assay and amplicor monitor assay.

OBJECTIVE: two standardized techniques, Quantiplex HCV RNA 2.0 (bDNA) and Amplicor Monitor, were evaluated for the quantification of hepatitis C virus (HCV) load. Our objectives were: 1) to determine the relationship between viral load and genotype, and 2) to evaluate viral load in serial serum samples and in patients with normal or slightly elevated liver enzyme values in an area with a high prevalence of genotype 1. RESULTS: the viral loads detected with the two methods correlated significantly (r = 0.7, p < 0.0001), but viral load was smaller with the Monitor than with the Quantiplex assay, and was independent of genotype. The Monitor/Quantiplex ratio was lower in patients with a non-1 genotype than in patients with genotype 1b. Virological characteristics were similar in patients with normal or slightly elevated enzyme levels and in patients with elevated enzyme values. Neither method showed a relationship between viral load and age, sex, duration of the infection, mode of transmission, or histological activity index. CONCLUSION: viral load was not dependent on genotype. Measurement of viral load in a single serum sample adequately reflected the viral load measured in several serum samples from patients with chronic HCV infection. Patients with normal liver enzyme levels are not good candidates, in virological terms, for treatment with interferon.

Adolescent↗
PubMed1999

[Early prediction of lack of response to treatment with interferon and interferon plus ribavirin using biochemical and virological criteria in patients with chronic hepatitis C].

The objectives of this study were the following: 1) to evaluate the predictive value of the detection of RNA-HVC compared to GPT in the third month of treatment in patients with chronic hepatitis C treated with IFN, and at the first and third month in patients treated with IFN and ribavirin for 6 and 12 months. The study included: A) 80/132 patients treated with IFN (3 MU/3 times a week for 6-12 months), and B) 70/110 patients who had previously not responded to IFN, and who were treated with combination therapy (IFN: standard dose, ribavirin: 1200 mg/day) for 6 months (n = 40) and 12 months (n = 30). In group A, the positive predictive value (the probability of predicting the lack of response if the RNA-HVC was positive or if the GPT was elevated at the third month) was greater for RNA-HVC than for GPT (97.9% vs. 94.4%), although the response was not unequivocal (2.3% vs. 10.5%). The negative predictive value was 48.6% vs. 36.2%, respectively. The prediction level (odds ratio) of RNA-HVC and of GPT was 39.7 vs. 8.78 (p <0.000001 vs. p <0.002). The positive predictive value was 97.6% in patients with genotype 1, 4 and 5, and 100% in those with genotype 2 and 3. In group B, the positive predictive value was also greater for RNA-HVC than for GPT at the first month (100% vs. 94.4%) following six months of therapy, the odds ratio being infinite vs. 7.6. The positive predictive value was greater for RNA-HVC at the third month than at the first (100% vs. 91%), whereas it was similar for GPT (100%) with 12 months of therapy, the odds ratio being greater for GPT than for RNA-HVC at the first month (infinite and 7.27). The following was concluded: 1) detection of RNA-HVC at the third month of treatment with IFN predicts in advance a lack of response in patients, with a minimum risk of error; 2) in patients with six months of combined therapy, the detection of RNA-HVC at the first month is extremely reliable in the prediction of a lack of response, whereas after 12 months of combined therapy, elevated GPT values at the first month and the detection of RNA-HVC at the third are highly predictive of a lack of response.

Adolescent↗
PubMed1998

Outcome of autoimmune hepatitis after liver transplantation.

BACKGROUND: Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis. The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation. METHODS: The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed. RESULTS: Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation. Sixteen patients were excluded from evaluation. Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6+/-1.5 years. Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P=0.0012) and were receiving less immunosuppressive treatment. The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation. None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P=0.059). Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4+/-1.06 years of follow-up after recurrence. CONCLUSIONS: Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.

Adult↗
PubMed1998

[Incidence of de novo neoplasms after liver transplantation].

BACKGROUND: De novo malignancy developing after transplantation constitutes a well-known complication or organ transplantation, mainly described among renal recipients. AIM: To determine the incidence of de novo internal malignancies (excluding therefore skin cancers and recurrent hepatocellular carcinoma) in a cohort of 183 patients undergoing liver transplantation (OLT) between 6/1/1991 and 12/1/1996 with a minimum follow-up of 12 months and under cyclosporine-azathioprine-prednisone. PATIENTS AND METHODS: The study comprised 183 patients (mean age: 53 [8] years, with 70% males) whose charts were reviewed retrospectively. Rejection, steroids treatment, methyl-prednisolone bolus and OKT3 use were compared in the cases and in the matched control group. RESULTS: Seven malignancies were detected: 3 lung carcinomas, 1 larynx, 1 prostate, 1 colon and 1 ovarian. The mean age was 53 (8) years. The diagnosis of cancer was made at an average time of 24 (17) months (range, 10-54) post-OLT. Three patients died with a mean survival of 31 (16) months. OLT indication was mainly for viral liver disease (5/7). Although not statistically significant, immunosuppression data were higher among patients with cancer than in the matched group. Two additional patients developed post-transplantation lymphoproliferative diseases at 2 and 9 months, respectively. CONCLUSION: We observed a wide variety of malignancies after OLT, but no associated factor was found, even though there was a trend to higher doses of immunosuppression in patients with cancers. The institution of preventive measures and surveillance programs may allow for early institution of therapy, improving therefore the survival.

Adult↗
PubMed1998

Interaction of the major epitope region of HIV protein gp41 with membrane model systems. A fluorescence spectroscopy study.

Fluorescence spectroscopy (both steady-state and time-resolved) was used to study the fragment 579-601 of gp41 ectodomain (HIV-1), a highly conserved sequence and major epitope, regarding (1) structural information, (2) interaction with membrane model systems, and (3) location in the phospholipid bilayer. The peptide was characterized both in its monomeric (after reduction of the disulfide bond between cysteine residues) and in the dimeric forms. The change of the fluorescence anisotropy between monomer and dimer was rationalized on the basis of energy migration, and a distance between the two tryptophan (Trp) residues of approximately 6 A was obtained. Using different fluorescence spectroscopy approaches, it was demonstrated that, despite the fact that monomeric gp41 fragment incorporates in the membrane model systems studied, the dimeric form does not interact with these vesicles. A methodology based on the increase of the mean fluorescence lifetime averaged by the preexponentials was derived, to obtain the partition coefficient of the peptide in the different lipid systems. Fluorescence quenching using lipophilic probes and red edge excitation shift (REES) were used to study the location of the gp41 fragment in the membrane. It was concluded that the Trp residue is located in a shallow position, near the interface. The REES results show an uncommonly large wavelength shift (18 nm) for the gp41 fragment incorporated in the membrane. Our results are consistent with a "two steps" model for the gp41 fusion mechanism similar to the one proposed for influenza virus hemagglutinin.

Amino Acid Sequence↗
PubMed1998

[Use of antihypertensive drugs in Spain, 1985-1995].

BACKGROUND: This study has analysed the trend of antihypertensive drugs consumption in Spain from 1985 to 1995, its economical impact and the correlation with the available scientific evidence. The utilization of calcium channel blockers in the context of the recent controversial about their safety profile was also evaluated. METHODS: Drugs from the ATC groups C02, C03 (excluding C03C), C07, C08 (excluding nimodipine and nicardipine) and C09 were included (ATC classification, 1996 version). Drug utilization data and cost figures were obtained from the databases ECOM and FAR-90 of the Ministry of Health. These databases contain the number of packages sold in community pharmacies that are charged to the National Health System. Data are expressed in defined daily doses per 1,000 inhabitants per day (DHD). The cost is expressed in current and constant pesetas. RESULTS: The use of antihypertensives increased from 34.78 DHD in 1985 to 103.55 DHD in 1995. Angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) are responsible for 89% of the total increase. Thiazides and beta-blockers showed a mild increase, although its relative contribution to the total figures declined from 72 to 32% at the end of the period. Rauwolfia alcaloids and antiadrenergic drugs sales were negligible (0.4% of total sales in 1995). Within the thiazides, consumption was concentrated in products containing > or = 50 mg hydrochlorothiazide or equivalent. Enalapril, captopril, nifedipine and the fixed-dose association of hydrochlorothiazide with amiloride were the most widely used drugs. The cost of antihypertensive drugs in current pesetas raised eight times through the study period reaching 105,501 millions pesetas in 1995; 89% of the cost corresponded to ACEI and CCB. Expressed in constant pesetas the cost increase was four fold. The recent controversia about CCB did not have influence on its consumption. CONCLUSIONS: The pattern of use of antihypertensive drugs in Spain does not follow the available scientific evidence. Drugs with less documented effectiveness are the most prescribed; even considering the same effectiveness, efficiency is lower for drugs with higher utilization rates. The available presentations for thiazides makes their utilization in the optimal dosification difficult.

Adrenergic Antagonists↗
PubMed1998

Tanycytes present in the adult rat mediobasal hypothalamus support the regeneration of monoaminergic axons.

We have recently shown that tanycytes present in the median eminence (ME) constitute a preferential support for the regeneration of lesioned neurohypophysial oxytocinergic and vasopressinergic axons. However, although tanycytes are particularly abundant in the ME, they are also present along the third ventricle wall. This study was thus undertaken to determine whether tanycytes present in the mediobasal hypothalamus overlying the ME were also able to support the regeneration of the numerous monoaminergic axons innervating this region. Using confocal laser scanning microscopy combined with double or triple fluorescence immunostaining, we have compared the relationships occurring between glial cells and lesioned catecholaminergic and serotonergic axons at the levels of surgical cuts placed in the dorsomedial hypothalamus devoid of tanycytes or in the ventromedial hypothalamus containing numerous tanycyte processes. In dorsal lesions, catecholaminergic and serotonergic transected fibers were found to abut onto the scar formed along the surgical cut and composed of closely inderdigitating astrocyte processes strongly immunoreactive for both glial fibrillary acidic protein (GFAP) and vimentin (VIM). In ventral lesions, the lesional scar was composed of GFAP-immunoreactive (IR) and VIM-IR astrocyte processes and of VIM-IR but GFAP-negative processes that were identified as tanycytic processes. In all the ventral lesions examined, numerous catecholaminergic and serotonergic fibers were found to regenerate into the surgical cut in association with the VIM-IR, GFAP-negative tanycyte processes. On the other hand, such regenerating fibers were never found in scar portions containing only GFAP-IR astrocytic structures. These data indicate that, like in the ME, tanycytes present in the mediobasal hypothalamus of adult rat provide a substrate that favors the regeneration of lesioned axons.

Age Factors↗
PubMed1998

Filipin-induced lesions in planar phospholipid bilayers imaged by atomic force microscopy.

Filipin is a macrolide polyene with antifungal activity belonging to the same family of antibiotics as amphotericin B and nystatin. Despite the spectroscopy and electron microscopy studies of its interaction with natural membranes and membrane model systems, several aspects of its biochemical action, such as the role of membrane sterols, remain to be completely understood. We have used atomic force microscopy (AFM) to study the effect of filipin on dipalmitoylphosphatidylethanolamine bilayers in the presence and absence of cholesterol. The bilayers were prepared by Langmuir-Blodgett deposition over mica and imaged under water. It was shown that filipin-induced lesions could only be found in membranes with cholesterol. In close agreement with electron microscopy results, we have reported the presence of densely packed circular protrusions in the membrane with a mean diameter of 19 nm (corrected for convolution with AFM tip) and 0.4 nm height. Larger circular protrusions (90 nm diameter and 2.5 nm height) and doughnut-shaped lesions were also detected. These results demonstrate that filipin-induced lesions in membranes previously observed by electron microscopy are not biased by artifacts resulting from sample preparation. Filipin aggregates in aqueous solution could also be imaged for the first time. These polydisperse spherical structures were observed in samples with and without cholesterol.

Cholesterol↗
PubMed1998

Early development of chronic active hepatitis in recurrent hepatitis C virus infection after liver transplantation: association with treatment of rejection.

BACKGROUND/AIMS: We retrospectively studied 63 consecutive patients (mean age 54+/-8) with hepatitis C virus genotype 1b recurrence after liver transplantation and with a minimum histological follow-up of 1 year, in order to determine whether an early severe recurrence, defined as the development of chronic active hepatitis within the first 2 years post-liver transplantation, was associated with increased immunosuppression. METHODS: The 1st year immunosuppression data (rejection episodes, boluses of methyl-prednisolone, cumulative doses of prednisone and azathioprine, OKT3 use) were recorded, and evaluated as predictive of severe recurrence at 1 and 2 years post-liver transplantation. Chronic active hepatitis and rejection were defined by histological criteria. Immunosuppression consisted of cyclosporine, azathioprine and prednisone. The treatment of rejection was based on a "bolus" of 1 g methyl-prednisolone/3 days. RESULTS: At 1 year, 64% (40/63) of the patients had chronic active hepatitis, whereas of the 40 patients who had a 2nd year biopsy available, 75% had chronic active hepatitis at 2 years. At 1 year post-liver transplantation, no significant association was observed between immunosuppression and the development of chronic active hepatitis. In contrast, at 2 years, rejection (p=0.006), treatment of rejection (p=0.05), methyl-prednisolone boluses (p=0.013) and the number of rejection episodes (p=0.0034) occurring during the 1st year post-liver transplantation were significantly more common in patients with chronic active hepatitis. There was also a trend towards higher cumulative steroids (9447+/-3176.5 vs 7891.5+/-2111 mg) and higher cumulative azathioprine doses (13472+/-11154 vs 6233.5+/-5937 mg) in patients with chronic active hepatitis as compared to those who did not develop chronic active hepatitis. CONCLUSIONS: Rejection and/or its treatment may accelerate the natural history of hepatitis C virus genotype 1b infection post-liver transplantation.

Alanine Transaminase↗